Periodontal disease is a risk factor for many systemic diseases such as Alzheimer’s disease and adverse pregnancy outcomes.Cleft palate(CP),the most common congenital craniofacial defect,has a multifaceted etiology i...Periodontal disease is a risk factor for many systemic diseases such as Alzheimer’s disease and adverse pregnancy outcomes.Cleft palate(CP),the most common congenital craniofacial defect,has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection.A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring.However,the precise relationship remains unclear.In this study,the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P.gingivalis injected intravenously and orally into pregnant mice.We investigated an obvious increasing CP(12.5%)in sonicated P.gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium.Then glycolysis and H4K12 lactylation(H4K12la)were detected to elevate in both mouse embryonic palatal mesenchyme(MEPM)cells and macrophages under P.gingivalis exposure which further promoted the transcription of metallopeptidase domain17(ADAM17),subsequently mediated the shedding of transforming growth factor-beta receptor 1(TGFBR1)in MEPM cells and mer tyrosine kinase(MerTK)in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate,eventually caused abnormalities in palate fusion and ossification.The abnormal efferocytosis also led to a predominance of M1 macrophages,which indirectly inhibited palatal osteogenesis via extracellular vesicles.Furthermore,pharmacological ADAM17 inhibition could ameliorate the abnormality of P.gingivalis-induced abnormal palate development.Therefore,our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.展开更多
The purpose of this study was to investigate the effect of vitamin B12 on palatal development by co-administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin （TCDD） and dexamethasone （DEX）. We examined the morphologic...The purpose of this study was to investigate the effect of vitamin B12 on palatal development by co-administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin （TCDD） and dexamethasone （DEX）. We examined the morphological and histological features of the palatal shelf and expression levels of key signaling molecules （trans- forming growth factor-β3 （TGF-β3） and TGF-β3 type I receptor （activin receptor-like kinase 5, ALK5）） during pala- togenesis among a control group （Group A）, TCDD＋DEX exposed group （Group B）, and TCDD＋DEX＋vitamin B12 exposed group （Group C）. While we failed to find that vitamin B12 decreased the incidence of cleft palate induced by TCDD＋DEX treatment, the expression levels of key signaling molecules （TGF-~3 and ALK5） during palatogenesis were significantly modulated. In TCDD＋DEX exposed and TCDD＋DEX＋vitamin B12 exposed groups, palatal shelves could not contact in the midline due to their small sizes. Our results suggest that vitamin B12 may inhibit the expression of some cleft palate inducers such as TGF-β3 and ALK5 in DEX＋TCDD exposed mice, which may be beneficial against palatogenesis to some degree, even though we were unable to observe a protective role of vitamin B12 in morphological and histological alterations of palatal shelves induced by DEX and TCDD.展开更多
Objective： To address the effect of intrinsic factors on craniofacial growth by analyzing the craniofacial morphology of unoperated isolated cleft palate in Chinese adult. Materials and Methods： This study included ...Objective： To address the effect of intrinsic factors on craniofacial growth by analyzing the craniofacial morphology of unoperated isolated cleft palate in Chinese adult. Materials and Methods： This study included 37 nonsyndromic isolated cleft palate and 39 age and gender matched non-clefts. Twenty-six cephalometric measurements were employed to evaluate the facial morphology. Independent samples T test and Mann- Whitney U were used for comparison. Significant difference was defined at 95% level. Results： Data from this study showed patients with unoperated isolated cleft palate have a reduced maxillary sagittal length （ANS-PMP, A-PMP, P〈0.05）, a smaller ANB angle （ANB, P〈0.05） and a retrusive ANS point （S-N-ANS, P〈0.05; Ba-N-ANS, P〈0.05）. Measurements descripted position of maxilla （S-Ptm, P〉0.05）, depth of bony pharynx （Ba-PMP, P〉0.05）, anterior and posterior maxillary height （N-ANS, P〉0.05; R-PMP, P〉0.05） and mandible morphology （including linear measurements and angle measurements） did not show any significant difference between case and control groups. Conclusions： Patients with isolated cleft palate were characterized by maxillary retrusion. Mandible morphology and cranial basal morphology in isolated cleft palate showed no significant difference with nonclefts. Patients with isolated cleft palate are more vulnerable to cross bite than nonclefts. Intrinsic deficiencies did detrimental effect on maxilla sagittal length, but did no detrimental effect on maxilla position, mandible size and position.展开更多
This study investigated the role of long non‐coding RNAs（lnc RNAs） in the development of the palatal tissues. Cleft palates in mice were induced by 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin（TCDD）. Expression levels ...This study investigated the role of long non‐coding RNAs（lnc RNAs） in the development of the palatal tissues. Cleft palates in mice were induced by 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin（TCDD）. Expression levels of long non‐coding RNA H19（lncR NA H19） and insulin‐like growth factor 2（IGF2） gene were measured by quantitative real‐time polymerase chain reaction（q RT‐PCR）. The rate of occurrence of cleft palate was found to be 100% by TCDD exposure, and TCDD could cause short upper limb, cerebral fissure, webbed neck, and short neck. The expression levels of lnc RNA H19 and IGF2 gene specifically showed embryo age‐related differences on E13, E14, and E15 in the palatal tissues. The expression levels of lnc RNA H19 and IGF2 gene showed an inverse relationship on E13, E14, and E15. These findings demonstrated that lnc RNA H19 and IGF2 can mediate the development of mouse cleft palate.展开更多
Objective To evaluate the effects of retinoic acid （RA） on expression of bone morphogenetic protein 7 （ BMP-7 ） in rat fetus with cleft palate, and the effects of RA on proliferation and apoptosis of osteoblasts. ...Objective To evaluate the effects of retinoic acid （RA） on expression of bone morphogenetic protein 7 （ BMP-7 ） in rat fetus with cleft palate, and the effects of RA on proliferation and apoptosis of osteoblasts. Methods All-trans RA （ATRA） was used to induce congenital cleft palate in Wistar rat. BMP-7 mRNA expression in maxillary bone tissue of fetal rats was measured by Northern blotting analysis. Flow cytometry and MTF assay were used to measure the apoptosis and proliferation of ATRA-treated MC-3T3-E1 cells. BMP-7 mRNA and protein expressions in ATRA-treated MC-3T3-E1 cells were detected by RT-PCR and Western blotting analysis. Remilts ATRA could induce cleft palate of rat fetus. The incidence rate of cleft palate induced by 100 mg/kg AT-RA （45.5%） was significantly higher than 50 mg/kg ATRA （ 12.5%, P 〈 0. 05 ）. BMP-7 mRNA expression decreased in maxillary bone tissue of rat fetus with cleft palate. MC-3T3-E1 cells proliferation treated with 1 × 10^-6 mol/L ATRA decreased by 60%, the cell apoptosis increased by 2 times. BMP-7 mRNA and protein levels in MC-3T3-E1 cells treated with 1 × 10^-6 mol/L ATRA decreased by 60% and 80%, respectively, compared with ATRA-untreated cells （ P 〈 0.05 ）. Conclusions BMP-7 may play an important role in embryonic palate development. RA may possess the ability to down-regulate cell proliferation through regulation of BMP-7 gene expression.展开更多
Objectives To identify the loci involved in nonsyndromic cleft lip with or without cleft palate （NSCL/P） in Northern Chinese people in Shenyang by using genomewide and interaction linkage scan.Methods Two multiplex ...Objectives To identify the loci involved in nonsyndromic cleft lip with or without cleft palate （NSCL/P） in Northern Chinese people in Shenyang by using genomewide and interaction linkage scan.Methods Two multiplex families in Shenyang from North China were ascertained through probands with NSCL/P.Blood of every member was drawn for DNA extraction and analysis.Genotypes were available for 382 autosomal short tandem repeat （STR） markers from the ABI Prism Linkage Mapping Set version 2.5.Linkage between markers and NSCL/P was assessed by 2-point parametric LOD scores,multipoint heterogeneity parametric LOD scores （HLODs）,and multipoint nonparametric linkage score （NPL）.Results The initial scan suggested linkage on Chromosomes 1,2,and 15.In subsequent fine mapping,1q32-q42 showed a maximum multipoint LOD score of 1.9（empirical P=0.013） and an NPL score of 2.35 （empirical P=0.053）.For 2p24-p25,the multipoint NPL increased to 2.94 （empirical P=0.007）.2-locus interaction analysis obtained a maximum NPL score of 3.73 （P=0.00078） and a maximum LOD score of 3 for Chromosome 1 （at 221 cM） and Chromosome 2 （at 29 cM）.Conclusion Both parametric and nonparametric linkage scores greatly increased over the initial linkage scores on 1q32-q42,suggesting a susceptibility locus in this region.Nonparametric linkage gave a strong evidence for a candidate region on chromosome 2p24-p25.The superiority of 2-locus linkage scores compared to single-locus scores gave additional evidence for linkage on 1q32-q42 and 2p24-p25,and suggested that certain genes in the two regions may contribute to NCSL/P risks with interaction.展开更多
Background and purpose The prenatal diagnosis of cleft palate is an important component of sequential therapy,but the relevant diagnostic methods are still limited.We aimed here,to explore the possibility of an early ...Background and purpose The prenatal diagnosis of cleft palate is an important component of sequential therapy,but the relevant diagnostic methods are still limited.We aimed here,to explore the possibility of an early prenatal diagnosis of cleft palate by assessing metabolites in pregnant mice.Methods Twenty-four inseminated females were randomly divided into retinoic acid(RA)-treated(treated with retinoic acid at 10.5 gestation days)and control groups.The metabolites of the embryonic palatal tissue,maternal amniotic fluid,and serum were characterized using 9.4T magnetic resonance spectroscopy in vitro.Then,a predictive model was established through the principal component analysis(PCA),and the correlations between the metabolites of amniotic fluid and palatal tissue were explored using orthogonal-2 partial least squares(O2-PLS).Results The incidences of cleft palate were 100%and 0%in the RA-treated and control groups,respectively.A predictive PCA model with a high specificity and sensitivity was established for the early prenatal diagnosis of isolated cleft palate using amniotic fluid metabolic data.Between RA-treated and control mice,we found that two metabolites in the amniotic fluid and palatal tissue were correlated.Creatinine showed the same trend in the palatal tissue and amniotic fluid,while choline showed opposite trends in the two tissues.However,the data for serum metabolites could not be used to establish a prediction model.Conclusion This study indicates that assessing the metabolites of amniotic fluid is a potential approach for the prenatal diagnosis of isolated cleft palate.展开更多
Aim Malonyl-CoA is regarded as a key signaling molecule in mammalian ceils. It is converted to acetyl-CoA, and to a lesser extent, to malonyl acid and malonylcamitine （C3DC）. Availability of carnitine has been repor...Aim Malonyl-CoA is regarded as a key signaling molecule in mammalian ceils. It is converted to acetyl-CoA, and to a lesser extent, to malonyl acid and malonylcamitine （C3DC）. Availability of carnitine has been reported to be essential for the developing fetus. The objectives of the present study were to analyze associations of malonylcarnitine, acetylcarnitine （C2）, and free carnitine （CO） in subjects with orofacial clefts. Methodology We performed a retrospective analysis of carnitine concentration obtained from a newborn screening program carried out in our institution. Concentrations of whole blood malonylcarnitine, acetylcarnitine, and free carnitine were measured using tandem mass spectrometry. The study group consisted of 51 children with nonsyndromic cleft lip with or without cleft palate. In total, 106 healthy children without congenital anomalies served as controls. Cut-off points were established using likeli-hood ratio values. Results The mean concentration of malonylcarnitine in the cleft group was lower than that of the control group, 0.048 μmol.L^1 vs. 0.058 μmol.L^-1, respectively （P=-0.009）. In patients with orofacial cleft, low malonylcarnitine levels （〈0.047 μmol.L-1） were 1.7 times more predominant than in healthy individuals （P=-0.03）. The mean concentration of acetylcarnitine was also lower in affected newborns in comparison to controls, 33.8 μol.L^-1 vs. 37.8 μmol·L^-1, respectively （P=-0.026）. After analysis of acetylearnitine and free carnitine concentrations, the likelihood ratio test did not indicate valuable cut-offpoints. Conclusion The study provides initial data indicating a potential association between decreased malonylcarnitine and abnormal palatogenesis.展开更多
Objective To establish an acoustic perceptual method analyzing the compensatory articulation errors in children with operated cleft palate via the formants of Chinese pure vowels. Methods The first three formants whic...Objective To establish an acoustic perceptual method analyzing the compensatory articulation errors in children with operated cleft palate via the formants of Chinese pure vowels. Methods The first three formants which represent vocal transmission character in Chinese pure vowels of 84 subjects with operated cleft palate, were measured by Computerized Speech Signal Processing System (CSSPS). The Chinese vowel graph of postoperative patients with cleft palate was stated by the first formant frequencies (F1) and the second formant frequencies (F2) of the Chinese pure vowels between the two groups. Results Values of F1 and F2 of vowels except [a] in the poor articulation group (Group A) were significantly different from those in the good articulation group (Group B) (P<0.05 or P<0.01). As compared with that in Group B, the vowel graph demonstrated the decreased perceptual distances in Group A. These findings indicated that there might still be the backward movements of tongue, perverted mandibular movements and disharmonious lip movements in addition to the velopharyngeal insufficiency (VPI) in Group A. Conclusion The speech articulation of children with repaired cleft palate should be gained by correcting the aberrant compensatory articulation errors in the condition of velopharyngeal competence. Computerized Speech Signal Processing System (CSSPS), which is regarded as the content of objective quantitative measurement, is a precise, simple, reliable and atroumatic technique for children with cleft palate to analyze pathological compensatory articulation errors.展开更多
Objective： Nonsyndromic cleft lip with or without cleft palate（NSCL/P） is a common birth defect with unclear etiology. Both genetic and environmental factors may contribute to NSCL/P. Many genes have been identifie...Objective： Nonsyndromic cleft lip with or without cleft palate（NSCL/P） is a common birth defect with unclear etiology. Both genetic and environmental factors may contribute to NSCL/P. Many genes have been identified as candidate genes associated with this disease. Interferon regulatory factor 6（IRF6） gene and transforming growth factor-a（TGFA） gene seem to be crucial in the predisposition of NSCL/ P. Here we evaluated some single nucleotide polymorphisms（SNPs） loci of TGFA and IRF6 genes in Chinese nuclear families consisting of fathers, mothers and affected offspring with NSCL/P. Methods：Fifty patients of NSCL/P were confirmed by the plastic surgeons. They and their parents were included in the study, all with the informed consents. SNPs loci of TGFA and IRF6 genes were analyzed by microarray technology. Some PCR products were randomly chosen and sequenced to check microarray results. The distribution of gene type and allele frequency between patient group and parents group were compared. Then a Haplotype Relative Risk（HRR） and Transmission Disequilibrium Test（TDT） were performed. Results：The sequences of randomly selected PCR products were all consistent with the microarray results. All loci were in Hardy-Weinberg equilibrium. There were no significant differences in the distribution of genotypes and alleles between patients and their parents. Using HRR and TDT analyses the V274I of IRF6 was associated with NSCL/P, while another SNP locus oflRF6 was not. Strong evidence of linkage disequilibrium was found between the 2 SNP loci of TGFA and disease with the HRR analysis, but not with the TDT analysis. Conclusion：Our study confirms the contribution of IRF6 in the etiology of NSCL/P in populations of Asian ancestry. The association of TGFA with NSCL/P requires further research.展开更多
<b><span>Introduction:</span></b><span> Cleft palate (CP) is a congenital dysmorphosis that results</span><span> from a failure of the palatal processes of the maxil...<b><span>Introduction:</span></b><span> Cleft palate (CP) is a congenital dysmorphosis that results</span><span> from a failure of the palatal processes of the maxillary buds and nasal septum to merge. The objectives of this study were to determine the frequency of complications of the modified Furlow technique and to evaluate its anatomical and functional outcomes.</span><span> </span><b><span>Materials and Method:</span></b><span> </span><span>This was a retrospective study that took place over a period of 4 years (from January 1</span><sup><span style="vertical-align:super;">st</span></sup><span>, 2015 to December 31</span><sup><span style="vertical-align:super;">th</span></sup><span>, 2018) in the Department of Odontostomatology and Maxillofacial Surgery at the National Hospital of Donka (Conakry, Guinea). Data retrieval consisted of records from patients operated on for cleft palate according to Furlow’s</span><span> </span><span>modified technique only. The operative technique consisted of marginal incisions of the cleft according to the technique of the double Z-plasty of Furlow. Subsequently, the defect created between the 2 flaps and the anterior edge of the cleft was filled by two fat masses of Bichat sutured to each other with Vicryl 3-0.</span><span> </span><span>Four years after surgery, the patients were recalled for an evaluation of the anatomical and functional results.</span><span> </span><b><span>Results:</span></b><span> 13 patients underwent surgical loading according to the modified Furlow technique. The average age of the patients was 6.9 years with an age range of 7 </span><span>months and 17 years. Females were the most affected, with 61.54% of cases</span><span> and a sex ratio of 0.62. The primary repair rate was 84.61% of cases. Immediate operative follow-up was simple with epithelialization of the flaps in all </span><span>patients. Four (4) years after the surgeries, 12 patients were reevaluated</span><span> (92.30%), among them one case (8.33%) of fistula complication was noted. The mobility of the veil and the phonation were good in 85.71% and 60% respectively. Ar</span><span>ticular disorders with nasonation were found in 2 patients (16.67%). Swallowing was normal in 85.72% of cases.</span><span> </span><b><span>Conclusion:</span></b><span> The modified Furlow technique is an important contribution to cleft palate surgery significantly</span><span> reducing the occurrence of postoperative complications. However, the delay </span><span>of the surgical operation remains a real obstacle for obtaining a normal </span><span>pho</span><span>nation.</span>展开更多
Objective Convincing evidence suggests a link between increased risk of nonsyndromic cleft lip with or without cleft palate （NSCL/P） and low intake of folic acid by the mother during pregnancy. The present study was...Objective Convincing evidence suggests a link between increased risk of nonsyndromic cleft lip with or without cleft palate （NSCL/P） and low intake of folic acid by the mother during pregnancy. The present study was designed to explore if genetic variation in the betaine‐homocysteine methyltransferase （BHMT） gene contributes to NSCL/P. Methods DNA was obtained from 166 individuals with NSCL/P and 285 healthy subjects. Three known single nucleotide polymorphisms （SNPs） present in the BHMT gene （rs651852, rs3797546, and rs3733890） were investigated by real‐time PCR‐based TaqMan genotyping. Results Neither allelic nor genotypic association was found between NSCL/P and SNPs rs651852 and rs3733890. SNP rs3797546 did not show allelic association with NSCL/P; however, a higher proportion of NSCL/P patients carry the CC genotype compared with the TT＋CT genotype （P=0.020, OR=2.10, 95% CI=1.11‐3.95）. Conclusion Our study suggests that polymorphism rs3797546 in the BHMT gene may confer genetic risk of NSCL/P in a recessive manner.展开更多
Background: In developing countries, charity cleft surgical mission is always operated by sporadic surgical teams without systematic follow up and quality assurance. In the past few decades, many mission projects have...Background: In developing countries, charity cleft surgical mission is always operated by sporadic surgical teams without systematic follow up and quality assurance. In the past few decades, many mission projects have been held regularly in China. The purpose of this audit was a retrospective analysis of a 9-year cleft lip and palate charity project operated in a tertiary hospital in China Shenzhen Area to evaluate perioperative and postoperative complications. Nevertheless, understanding the risk profile is essential for establishing a sustainable in-house cleft service in Shenzhen. Methods: A detailed analysis of hospital centralized record in the The University of Hong Kong-Shenzhen Hospital (HKUSZH) was reviewed since the first charity project held in 2015. The parameters of this audit were focused on perioperative complications including anesthesia related problems, early postoperative complications in patients who underwent primary or secondary cleft surgeries. A total of 430 consecutive admitted cases of 311 non-syndromic cleft lip & palate patients were enrolled into the charity project from June 2015 to July 2024. The main anesthesia related complications that occurred during general anesthesia were respiratory tract problems, while intraoperative complication was excessive bleeding, so as wound local infection and reaction were the main early postoperative complications. Results: In our 9-year clinical audit of 430 cleft lip and palate charity surgeries in Shenzhen, we observed no mortalities and a anesthesia-related complication rate of 1.16%. Specific intraoperative complications included excessive bleeding, while early postoperative issues were dominated by wound infections. The fistula rate of 18.7% post palate repair and the average hospital stay of 3.71 days complete the profile of our surgical outcomes. These data underscore the project’s efficacy and offer a reference for international cleft missions aiming for safe and efficient surgical care. Conclusions: This study provides a thorough data review of the complications in the past 9 years charity missions for cleft lip and palate surgery in a well-structured hospital infrastructure and logistic support by local surgical team. There were no perioperative or postoperative death during the study period and the overall short-term complication rate was low. Therefore, it could be a reference model for other international cleft mission in developing country for a safe and efficient service in future.展开更多
Non-syndromic cleft lip with or without cleft palate （nsCL/P） is among the most common major birth defects, with complex inheritance involving multiple genes and environmental factors. Numerous studies of MTHFR, enc...Non-syndromic cleft lip with or without cleft palate （nsCL/P） is among the most common major birth defects, with complex inheritance involving multiple genes and environmental factors. Numerous studies of MTHFR, encoding methylenetetrahydrofolate reductase, which catalyzes the rate-limiting step of folic acid biosynthesis, have shown inconsistent association of two common hypomorphic allelic variants, C677T and A1298C, in nsCL/P patients and, in some cases, their mothers. We have studied the MTHFR C677T and A1298C polymorphisms in nsCL/P patients, their mothers, and population-matched controls from northern Venezuela. We found no evidence for contribution of the MTHFR C677T and A1298C variants to the risk of nsCL/P in northern Venezuela. Overall, our findings fail to support a causal role of either the MTHFR C677T or A 1298C variants in the pathogenesis of nsCL/P in northern Venezuela.展开更多
Background The receptor tyrosine kinase-like orphan receptor 2 （ROR2） gene has been recently shown to play important roles in palatal development in animal models and resides in the chromosomal region linked to non ...Background The receptor tyrosine kinase-like orphan receptor 2 （ROR2） gene has been recently shown to play important roles in palatal development in animal models and resides in the chromosomal region linked to non syndromic cleft lip with or without cleft palate in humans.The aim of this study was to investigate the possible association between ROR2 gene and non-syndromic oral clefts.Methods Here we tested 38 eligible single-nucleotide polymorphisms （SNPs） in ROR2 gene in 297 non-syndromic cleft lip with or without cleft palate and in 82 non-syndromic cleft palate case parent trios recruited from Asia and Maryland.Family Based Association Test was used to test for deviation from Mendelian inheritance.Plink software was used to test potential parent of origin effect.Possible maternally mediated in utero effects were assessed using the TRlad Multi-Marker approach under an assumption of mating symmetry in the population.Results Significant evidence of linkage and association was shown for 3 SNPs （rs7858435,rs10820914 and rs3905385） among 57 Asian non-syndromic cleft palate trios in Family Based Association Tests.P values for these 3 SNPs equaled to 0.000068,0.000115 and 0.000464 respectively which were all less than the significance level （0.05/38=0.0013） adjusted by strict Bonferroni correction.Relevant odds ratios for the risk allele were 3.42 （1.80-6.50）,3.45 （1.75-6.67） and 2.94 （1.56-5.56）,respectively.Statistical evidence of linkage and association was not shown for study groups other than non-syndromic cleft palate.Neither evidence for parent-of-origin nor maternal genotypic effect was shown for any of the ROR2 markers in our analysis for all study groups.Conclusion Our results provided evidence of linkage and association between the ROR2 gene and a gene controlling risk to non-syndromic cleft palate.展开更多
Cleft lip with or without cleft palate(CP) is one of the most common congenital malformations. Ultrasonographers involved in the routine 20-wk ultrasound screening could encounter these malformations. The face and pal...Cleft lip with or without cleft palate(CP) is one of the most common congenital malformations. Ultrasonographers involved in the routine 20-wk ultrasound screening could encounter these malformations. The face and palate develop in a very characteristic way. For ultrasonographers involved in screening these patients it is crucial to have a thorough understanding of the embryology of the face. This could help them to make a more accurate diagnosis and save time during the ultrasound. Subsequently, the current postnatal classification will be discussed to facilitate the communication with the CP teams.展开更多
The acoustic characteristics or the chinese vowels of 24 children with cleft palate and 10 normal control children were analyzed by computerized speech signal processing system (CSSPS),and the speech articulation was ...The acoustic characteristics or the chinese vowels of 24 children with cleft palate and 10 normal control children were analyzed by computerized speech signal processing system (CSSPS),and the speech articulation was judged with Glossary of clert palate speech(GCPS).The listening judgement showed that the speech articulation was significantly different between the two groups(P<0.01).The objective quantitative measurement suggested that the formant pattern(FP)of vowels in children with cleft palate was different from that of normal control children except vowel[a](P< 0.05).The acoustic vowelgraph or the Chinese vowels which demonstrated directly the relationship of vocal space and speech perception was stated with the first formant frequence(F1)and the second formant frequence(F2).The authors conclude that the values or F1 and F2 point out the upward and backward tongue movement to close the clert, which reflects the vocal characteristics of trausmission of clert palate speech.展开更多
An objective method, using a multi-band analysis technique, was proposed for analyzing plosive consonants in cleft palate speech. At first, the speech signal is decomposed in frequency domain using an auditory filter-...An objective method, using a multi-band analysis technique, was proposed for analyzing plosive consonants in cleft palate speech. At first, the speech signal is decomposed in frequency domain using an auditory filter-bank. Then, the sample-based features, namely cumulative energy and its increment speed, in each band were computed. Finally, using principle component analysis, these features were fused into one combined feature vector for assessment. Since the algorithm is based on perceptual properties of human auditory ear using non-uniform and multi-band analysis, the improvements of the consistence between the proposed approach and subjective evaluation are obtained.展开更多
Orofacial clefts (OFCs) are the most common congenital craniofacial disorders, of which the etiology is closely related to rare coding variants. Filamin B (FLNB) is an actin-binding protein implicated in bone formatio...Orofacial clefts (OFCs) are the most common congenital craniofacial disorders, of which the etiology is closely related to rare coding variants. Filamin B (FLNB) is an actin-binding protein implicated in bone formation. FLNB mutations have been identified in several types of syndromic OFCs and previous studies suggest a role of FLNB in the onset of non-syndromic OFCs (NSOFCs). Here, we report two rare heterozygous variants (p.P441T and p.G565R) in FLNB in two unrelated hereditary families with NSOFCs. Bioinformatics analysis suggests that both variants may disrupt the function of FLNB. In mammalian cells, p.P441T and p.G565R variants are less potent to induce cell stretches than wild type FLNB, suggesting that they are loss-of-function mutations. Immunohistochemistry analysis demonstrates that FLNB is abundantly expressed during palatal development. Importantly, Flnb^(−/−) embryos display cleft palates and previously defined skeletal defects. Taken together, our findings reveal that FLNB is required for development of palates in mice and FLNB is a bona fide causal gene for NSOFCs in humans.展开更多
基金funded by grants from the National Natural Science Foundation of China(grant numbers 82170912 and 82370910)the Beijing Stomatological Hospital,Capital Medical University Young Scientist Program(No.YSP202404).
文摘Periodontal disease is a risk factor for many systemic diseases such as Alzheimer’s disease and adverse pregnancy outcomes.Cleft palate(CP),the most common congenital craniofacial defect,has a multifaceted etiology influenced by complex genetic and environmental risk factors such as maternal bacterial or virus infection.A prior case-control study revealed a surprisingly strong association between maternal periodontal disease and CP in offspring.However,the precise relationship remains unclear.In this study,the relationship between maternal oral pathogen and CP in offspring was studied by sonicated P.gingivalis injected intravenously and orally into pregnant mice.We investigated an obvious increasing CP(12.5%)in sonicated P.gingivalis group which had inhibited osteogenesis in mesenchyme and blocked efferocytosis in epithelium.Then glycolysis and H4K12 lactylation(H4K12la)were detected to elevate in both mouse embryonic palatal mesenchyme(MEPM)cells and macrophages under P.gingivalis exposure which further promoted the transcription of metallopeptidase domain17(ADAM17),subsequently mediated the shedding of transforming growth factor-beta receptor 1(TGFBR1)in MEPM cells and mer tyrosine kinase(MerTK)in macrophages and resulted in the suppression of efferocytosis and osteogenesis in palate,eventually caused abnormalities in palate fusion and ossification.The abnormal efferocytosis also led to a predominance of M1 macrophages,which indirectly inhibited palatal osteogenesis via extracellular vesicles.Furthermore,pharmacological ADAM17 inhibition could ameliorate the abnormality of P.gingivalis-induced abnormal palate development.Therefore,our study extends the knowledge of how maternal oral pathogen affects fetal palate development and provides a novel perspective to understand the pathogenesis of CP.
基金Project supported by thc National Natural Science Foundation of China （Nos. 81000425 and 30530730） and the Sichuan Key Tech- nology R＆D Program （No. 2010SZ0098）, China
文摘The purpose of this study was to investigate the effect of vitamin B12 on palatal development by co-administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin （TCDD） and dexamethasone （DEX）. We examined the morphological and histological features of the palatal shelf and expression levels of key signaling molecules （trans- forming growth factor-β3 （TGF-β3） and TGF-β3 type I receptor （activin receptor-like kinase 5, ALK5）） during pala- togenesis among a control group （Group A）, TCDD＋DEX exposed group （Group B）, and TCDD＋DEX＋vitamin B12 exposed group （Group C）. While we failed to find that vitamin B12 decreased the incidence of cleft palate induced by TCDD＋DEX treatment, the expression levels of key signaling molecules （TGF-~3 and ALK5） during palatogenesis were significantly modulated. In TCDD＋DEX exposed and TCDD＋DEX＋vitamin B12 exposed groups, palatal shelves could not contact in the midline due to their small sizes. Our results suggest that vitamin B12 may inhibit the expression of some cleft palate inducers such as TGF-β3 and ALK5 in DEX＋TCDD exposed mice, which may be beneficial against palatogenesis to some degree, even though we were unable to observe a protective role of vitamin B12 in morphological and histological alterations of palatal shelves induced by DEX and TCDD.
文摘Objective： To address the effect of intrinsic factors on craniofacial growth by analyzing the craniofacial morphology of unoperated isolated cleft palate in Chinese adult. Materials and Methods： This study included 37 nonsyndromic isolated cleft palate and 39 age and gender matched non-clefts. Twenty-six cephalometric measurements were employed to evaluate the facial morphology. Independent samples T test and Mann- Whitney U were used for comparison. Significant difference was defined at 95% level. Results： Data from this study showed patients with unoperated isolated cleft palate have a reduced maxillary sagittal length （ANS-PMP, A-PMP, P〈0.05）, a smaller ANB angle （ANB, P〈0.05） and a retrusive ANS point （S-N-ANS, P〈0.05; Ba-N-ANS, P〈0.05）. Measurements descripted position of maxilla （S-Ptm, P〉0.05）, depth of bony pharynx （Ba-PMP, P〉0.05）, anterior and posterior maxillary height （N-ANS, P〉0.05; R-PMP, P〉0.05） and mandible morphology （including linear measurements and angle measurements） did not show any significant difference between case and control groups. Conclusions： Patients with isolated cleft palate were characterized by maxillary retrusion. Mandible morphology and cranial basal morphology in isolated cleft palate showed no significant difference with nonclefts. Patients with isolated cleft palate are more vulnerable to cross bite than nonclefts. Intrinsic deficiencies did detrimental effect on maxilla sagittal length, but did no detrimental effect on maxilla position, mandible size and position.
基金supported by the grants of the National Natural Science Foundation of China(81502843)college students’research and innovation program of Xinxiang Medical UniversityHenan Province Xinxiang Key Laboratory of medical tissue regeneration program
文摘This study investigated the role of long non‐coding RNAs（lnc RNAs） in the development of the palatal tissues. Cleft palates in mice were induced by 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin（TCDD）. Expression levels of long non‐coding RNA H19（lncR NA H19） and insulin‐like growth factor 2（IGF2） gene were measured by quantitative real‐time polymerase chain reaction（q RT‐PCR）. The rate of occurrence of cleft palate was found to be 100% by TCDD exposure, and TCDD could cause short upper limb, cerebral fissure, webbed neck, and short neck. The expression levels of lnc RNA H19 and IGF2 gene specifically showed embryo age‐related differences on E13, E14, and E15 in the palatal tissues. The expression levels of lnc RNA H19 and IGF2 gene showed an inverse relationship on E13, E14, and E15. These findings demonstrated that lnc RNA H19 and IGF2 can mediate the development of mouse cleft palate.
基金Supported by National Natural Science Foundation of China(30500414)Scientific Research Project in Department of Education of Liaoning Province(05L508,20061010)
文摘Objective To evaluate the effects of retinoic acid （RA） on expression of bone morphogenetic protein 7 （ BMP-7 ） in rat fetus with cleft palate, and the effects of RA on proliferation and apoptosis of osteoblasts. Methods All-trans RA （ATRA） was used to induce congenital cleft palate in Wistar rat. BMP-7 mRNA expression in maxillary bone tissue of fetal rats was measured by Northern blotting analysis. Flow cytometry and MTF assay were used to measure the apoptosis and proliferation of ATRA-treated MC-3T3-E1 cells. BMP-7 mRNA and protein expressions in ATRA-treated MC-3T3-E1 cells were detected by RT-PCR and Western blotting analysis. Remilts ATRA could induce cleft palate of rat fetus. The incidence rate of cleft palate induced by 100 mg/kg AT-RA （45.5%） was significantly higher than 50 mg/kg ATRA （ 12.5%, P 〈 0. 05 ）. BMP-7 mRNA expression decreased in maxillary bone tissue of rat fetus with cleft palate. MC-3T3-E1 cells proliferation treated with 1 × 10^-6 mol/L ATRA decreased by 60%, the cell apoptosis increased by 2 times. BMP-7 mRNA and protein levels in MC-3T3-E1 cells treated with 1 × 10^-6 mol/L ATRA decreased by 60% and 80%, respectively, compared with ATRA-untreated cells （ P 〈 0.05 ）. Conclusions BMP-7 may play an important role in embryonic palate development. RA may possess the ability to down-regulate cell proliferation through regulation of BMP-7 gene expression.
基金supported by National Natural Science Foundation of China (the research to identify susceptibility genes of nonsyndromic cleft lip and/or palates, 30600676)Program for New Century Excellent Talents of the Ministry of Education of China (NCET-07-0034)
文摘Objectives To identify the loci involved in nonsyndromic cleft lip with or without cleft palate （NSCL/P） in Northern Chinese people in Shenyang by using genomewide and interaction linkage scan.Methods Two multiplex families in Shenyang from North China were ascertained through probands with NSCL/P.Blood of every member was drawn for DNA extraction and analysis.Genotypes were available for 382 autosomal short tandem repeat （STR） markers from the ABI Prism Linkage Mapping Set version 2.5.Linkage between markers and NSCL/P was assessed by 2-point parametric LOD scores,multipoint heterogeneity parametric LOD scores （HLODs）,and multipoint nonparametric linkage score （NPL）.Results The initial scan suggested linkage on Chromosomes 1,2,and 15.In subsequent fine mapping,1q32-q42 showed a maximum multipoint LOD score of 1.9（empirical P=0.013） and an NPL score of 2.35 （empirical P=0.053）.For 2p24-p25,the multipoint NPL increased to 2.94 （empirical P=0.007）.2-locus interaction analysis obtained a maximum NPL score of 3.73 （P=0.00078） and a maximum LOD score of 3 for Chromosome 1 （at 221 cM） and Chromosome 2 （at 29 cM）.Conclusion Both parametric and nonparametric linkage scores greatly increased over the initial linkage scores on 1q32-q42,suggesting a susceptibility locus in this region.Nonparametric linkage gave a strong evidence for a candidate region on chromosome 2p24-p25.The superiority of 2-locus linkage scores compared to single-locus scores gave additional evidence for linkage on 1q32-q42 and 2p24-p25,and suggested that certain genes in the two regions may contribute to NCSL/P risks with interaction.
基金This study was funded by the Guangdong Basic and Applied Basic Research Foundation(2019A1515011857)the Guangdong Medical Research Foundation Project(A2019108,A2020099,A2020538)+4 种基金the Guangdong Science and Technology Innovation Strategy Special Fund(Vertical Collaborative Management Direction)Project([2018]157-45)the Guangdong Higher Education Teaching Reform Project(No.246),the Shantou University Chuangqiang Provincial Special Fund Construction Project(925-38230120)the Shantou University Special Support for In-school Research of the School of Arts(STURCS201813)and the Shantou Science and Technology Project([2019]10602)It was also supported by the Department of Education of Guangdong Province under the Top-tier University Development Scheme for Research and Control of Infectious Diseases and the grant for Key Disciplinary Project of Clinical Medicine under the Guangdong Highlevel University Development Program,and supported by 2020 Li Ka Shing Foundation Cross-Disciplinary Research Grant(2020LKSFG18B,2020LKSFG02E).
文摘Background and purpose The prenatal diagnosis of cleft palate is an important component of sequential therapy,but the relevant diagnostic methods are still limited.We aimed here,to explore the possibility of an early prenatal diagnosis of cleft palate by assessing metabolites in pregnant mice.Methods Twenty-four inseminated females were randomly divided into retinoic acid(RA)-treated(treated with retinoic acid at 10.5 gestation days)and control groups.The metabolites of the embryonic palatal tissue,maternal amniotic fluid,and serum were characterized using 9.4T magnetic resonance spectroscopy in vitro.Then,a predictive model was established through the principal component analysis(PCA),and the correlations between the metabolites of amniotic fluid and palatal tissue were explored using orthogonal-2 partial least squares(O2-PLS).Results The incidences of cleft palate were 100%and 0%in the RA-treated and control groups,respectively.A predictive PCA model with a high specificity and sensitivity was established for the early prenatal diagnosis of isolated cleft palate using amniotic fluid metabolic data.Between RA-treated and control mice,we found that two metabolites in the amniotic fluid and palatal tissue were correlated.Creatinine showed the same trend in the palatal tissue and amniotic fluid,while choline showed opposite trends in the two tissues.However,the data for serum metabolites could not be used to establish a prediction model.Conclusion This study indicates that assessing the metabolites of amniotic fluid is a potential approach for the prenatal diagnosis of isolated cleft palate.
文摘Aim Malonyl-CoA is regarded as a key signaling molecule in mammalian ceils. It is converted to acetyl-CoA, and to a lesser extent, to malonyl acid and malonylcamitine （C3DC）. Availability of carnitine has been reported to be essential for the developing fetus. The objectives of the present study were to analyze associations of malonylcarnitine, acetylcarnitine （C2）, and free carnitine （CO） in subjects with orofacial clefts. Methodology We performed a retrospective analysis of carnitine concentration obtained from a newborn screening program carried out in our institution. Concentrations of whole blood malonylcarnitine, acetylcarnitine, and free carnitine were measured using tandem mass spectrometry. The study group consisted of 51 children with nonsyndromic cleft lip with or without cleft palate. In total, 106 healthy children without congenital anomalies served as controls. Cut-off points were established using likeli-hood ratio values. Results The mean concentration of malonylcarnitine in the cleft group was lower than that of the control group, 0.048 μmol.L^1 vs. 0.058 μmol.L^-1, respectively （P=-0.009）. In patients with orofacial cleft, low malonylcarnitine levels （〈0.047 μmol.L-1） were 1.7 times more predominant than in healthy individuals （P=-0.03）. The mean concentration of acetylcarnitine was also lower in affected newborns in comparison to controls, 33.8 μol.L^-1 vs. 37.8 μmol·L^-1, respectively （P=-0.026）. After analysis of acetylearnitine and free carnitine concentrations, the likelihood ratio test did not indicate valuable cut-offpoints. Conclusion The study provides initial data indicating a potential association between decreased malonylcarnitine and abnormal palatogenesis.
基金this work was supported by the Natural Science Foundation of Shaanxi Province (No98SM65)
文摘Objective To establish an acoustic perceptual method analyzing the compensatory articulation errors in children with operated cleft palate via the formants of Chinese pure vowels. Methods The first three formants which represent vocal transmission character in Chinese pure vowels of 84 subjects with operated cleft palate, were measured by Computerized Speech Signal Processing System (CSSPS). The Chinese vowel graph of postoperative patients with cleft palate was stated by the first formant frequencies (F1) and the second formant frequencies (F2) of the Chinese pure vowels between the two groups. Results Values of F1 and F2 of vowels except [a] in the poor articulation group (Group A) were significantly different from those in the good articulation group (Group B) (P<0.05 or P<0.01). As compared with that in Group B, the vowel graph demonstrated the decreased perceptual distances in Group A. These findings indicated that there might still be the backward movements of tongue, perverted mandibular movements and disharmonious lip movements in addition to the velopharyngeal insufficiency (VPI) in Group A. Conclusion The speech articulation of children with repaired cleft palate should be gained by correcting the aberrant compensatory articulation errors in the condition of velopharyngeal competence. Computerized Speech Signal Processing System (CSSPS), which is regarded as the content of objective quantitative measurement, is a precise, simple, reliable and atroumatic technique for children with cleft palate to analyze pathological compensatory articulation errors.
基金supported by the Medical Technology Development Foundation of Jiangsu Provincial Health Bureau of China (H200513)Changjiang Scholars and Innovative Research Team in University (IRT0631) and National 973 Program(2006CB944005)
文摘Objective： Nonsyndromic cleft lip with or without cleft palate（NSCL/P） is a common birth defect with unclear etiology. Both genetic and environmental factors may contribute to NSCL/P. Many genes have been identified as candidate genes associated with this disease. Interferon regulatory factor 6（IRF6） gene and transforming growth factor-a（TGFA） gene seem to be crucial in the predisposition of NSCL/ P. Here we evaluated some single nucleotide polymorphisms（SNPs） loci of TGFA and IRF6 genes in Chinese nuclear families consisting of fathers, mothers and affected offspring with NSCL/P. Methods：Fifty patients of NSCL/P were confirmed by the plastic surgeons. They and their parents were included in the study, all with the informed consents. SNPs loci of TGFA and IRF6 genes were analyzed by microarray technology. Some PCR products were randomly chosen and sequenced to check microarray results. The distribution of gene type and allele frequency between patient group and parents group were compared. Then a Haplotype Relative Risk（HRR） and Transmission Disequilibrium Test（TDT） were performed. Results：The sequences of randomly selected PCR products were all consistent with the microarray results. All loci were in Hardy-Weinberg equilibrium. There were no significant differences in the distribution of genotypes and alleles between patients and their parents. Using HRR and TDT analyses the V274I of IRF6 was associated with NSCL/P, while another SNP locus oflRF6 was not. Strong evidence of linkage disequilibrium was found between the 2 SNP loci of TGFA and disease with the HRR analysis, but not with the TDT analysis. Conclusion：Our study confirms the contribution of IRF6 in the etiology of NSCL/P in populations of Asian ancestry. The association of TGFA with NSCL/P requires further research.
文摘<b><span>Introduction:</span></b><span> Cleft palate (CP) is a congenital dysmorphosis that results</span><span> from a failure of the palatal processes of the maxillary buds and nasal septum to merge. The objectives of this study were to determine the frequency of complications of the modified Furlow technique and to evaluate its anatomical and functional outcomes.</span><span> </span><b><span>Materials and Method:</span></b><span> </span><span>This was a retrospective study that took place over a period of 4 years (from January 1</span><sup><span style="vertical-align:super;">st</span></sup><span>, 2015 to December 31</span><sup><span style="vertical-align:super;">th</span></sup><span>, 2018) in the Department of Odontostomatology and Maxillofacial Surgery at the National Hospital of Donka (Conakry, Guinea). Data retrieval consisted of records from patients operated on for cleft palate according to Furlow’s</span><span> </span><span>modified technique only. The operative technique consisted of marginal incisions of the cleft according to the technique of the double Z-plasty of Furlow. Subsequently, the defect created between the 2 flaps and the anterior edge of the cleft was filled by two fat masses of Bichat sutured to each other with Vicryl 3-0.</span><span> </span><span>Four years after surgery, the patients were recalled for an evaluation of the anatomical and functional results.</span><span> </span><b><span>Results:</span></b><span> 13 patients underwent surgical loading according to the modified Furlow technique. The average age of the patients was 6.9 years with an age range of 7 </span><span>months and 17 years. Females were the most affected, with 61.54% of cases</span><span> and a sex ratio of 0.62. The primary repair rate was 84.61% of cases. Immediate operative follow-up was simple with epithelialization of the flaps in all </span><span>patients. Four (4) years after the surgeries, 12 patients were reevaluated</span><span> (92.30%), among them one case (8.33%) of fistula complication was noted. The mobility of the veil and the phonation were good in 85.71% and 60% respectively. Ar</span><span>ticular disorders with nasonation were found in 2 patients (16.67%). Swallowing was normal in 85.72% of cases.</span><span> </span><b><span>Conclusion:</span></b><span> The modified Furlow technique is an important contribution to cleft palate surgery significantly</span><span> reducing the occurrence of postoperative complications. However, the delay </span><span>of the surgical operation remains a real obstacle for obtaining a normal </span><span>pho</span><span>nation.</span>
基金supported by the National Natural Science Foundation of China (grant number 307009907)Beijing Natural Science Foundation (grant number 7082038)Beijing Foundation for Excellent Elite (grant number 2010D003034000013)
文摘Objective Convincing evidence suggests a link between increased risk of nonsyndromic cleft lip with or without cleft palate （NSCL/P） and low intake of folic acid by the mother during pregnancy. The present study was designed to explore if genetic variation in the betaine‐homocysteine methyltransferase （BHMT） gene contributes to NSCL/P. Methods DNA was obtained from 166 individuals with NSCL/P and 285 healthy subjects. Three known single nucleotide polymorphisms （SNPs） present in the BHMT gene （rs651852, rs3797546, and rs3733890） were investigated by real‐time PCR‐based TaqMan genotyping. Results Neither allelic nor genotypic association was found between NSCL/P and SNPs rs651852 and rs3733890. SNP rs3797546 did not show allelic association with NSCL/P; however, a higher proportion of NSCL/P patients carry the CC genotype compared with the TT＋CT genotype （P=0.020, OR=2.10, 95% CI=1.11‐3.95）. Conclusion Our study suggests that polymorphism rs3797546 in the BHMT gene may confer genetic risk of NSCL/P in a recessive manner.
文摘Background: In developing countries, charity cleft surgical mission is always operated by sporadic surgical teams without systematic follow up and quality assurance. In the past few decades, many mission projects have been held regularly in China. The purpose of this audit was a retrospective analysis of a 9-year cleft lip and palate charity project operated in a tertiary hospital in China Shenzhen Area to evaluate perioperative and postoperative complications. Nevertheless, understanding the risk profile is essential for establishing a sustainable in-house cleft service in Shenzhen. Methods: A detailed analysis of hospital centralized record in the The University of Hong Kong-Shenzhen Hospital (HKUSZH) was reviewed since the first charity project held in 2015. The parameters of this audit were focused on perioperative complications including anesthesia related problems, early postoperative complications in patients who underwent primary or secondary cleft surgeries. A total of 430 consecutive admitted cases of 311 non-syndromic cleft lip & palate patients were enrolled into the charity project from June 2015 to July 2024. The main anesthesia related complications that occurred during general anesthesia were respiratory tract problems, while intraoperative complication was excessive bleeding, so as wound local infection and reaction were the main early postoperative complications. Results: In our 9-year clinical audit of 430 cleft lip and palate charity surgeries in Shenzhen, we observed no mortalities and a anesthesia-related complication rate of 1.16%. Specific intraoperative complications included excessive bleeding, while early postoperative issues were dominated by wound infections. The fistula rate of 18.7% post palate repair and the average hospital stay of 3.71 days complete the profile of our surgical outcomes. These data underscore the project’s efficacy and offer a reference for international cleft missions aiming for safe and efficient surgical care. Conclusions: This study provides a thorough data review of the complications in the past 9 years charity missions for cleft lip and palate surgery in a well-structured hospital infrastructure and logistic support by local surgical team. There were no perioperative or postoperative death during the study period and the overall short-term complication rate was low. Therefore, it could be a reference model for other international cleft mission in developing country for a safe and efficient service in future.
基金supported by the grant DE13571 from the National Institutes of Health (R.A.S.),USAthe support from Rotaplast International, Inc. (M.M.T.),USA
文摘Non-syndromic cleft lip with or without cleft palate （nsCL/P） is among the most common major birth defects, with complex inheritance involving multiple genes and environmental factors. Numerous studies of MTHFR, encoding methylenetetrahydrofolate reductase, which catalyzes the rate-limiting step of folic acid biosynthesis, have shown inconsistent association of two common hypomorphic allelic variants, C677T and A1298C, in nsCL/P patients and, in some cases, their mothers. We have studied the MTHFR C677T and A1298C polymorphisms in nsCL/P patients, their mothers, and population-matched controls from northern Venezuela. We found no evidence for contribution of the MTHFR C677T and A1298C variants to the risk of nsCL/P in northern Venezuela. Overall, our findings fail to support a causal role of either the MTHFR C677T or A 1298C variants in the pathogenesis of nsCL/P in northern Venezuela.
文摘Background The receptor tyrosine kinase-like orphan receptor 2 （ROR2） gene has been recently shown to play important roles in palatal development in animal models and resides in the chromosomal region linked to non syndromic cleft lip with or without cleft palate in humans.The aim of this study was to investigate the possible association between ROR2 gene and non-syndromic oral clefts.Methods Here we tested 38 eligible single-nucleotide polymorphisms （SNPs） in ROR2 gene in 297 non-syndromic cleft lip with or without cleft palate and in 82 non-syndromic cleft palate case parent trios recruited from Asia and Maryland.Family Based Association Test was used to test for deviation from Mendelian inheritance.Plink software was used to test potential parent of origin effect.Possible maternally mediated in utero effects were assessed using the TRlad Multi-Marker approach under an assumption of mating symmetry in the population.Results Significant evidence of linkage and association was shown for 3 SNPs （rs7858435,rs10820914 and rs3905385） among 57 Asian non-syndromic cleft palate trios in Family Based Association Tests.P values for these 3 SNPs equaled to 0.000068,0.000115 and 0.000464 respectively which were all less than the significance level （0.05/38=0.0013） adjusted by strict Bonferroni correction.Relevant odds ratios for the risk allele were 3.42 （1.80-6.50）,3.45 （1.75-6.67） and 2.94 （1.56-5.56）,respectively.Statistical evidence of linkage and association was not shown for study groups other than non-syndromic cleft palate.Neither evidence for parent-of-origin nor maternal genotypic effect was shown for any of the ROR2 markers in our analysis for all study groups.Conclusion Our results provided evidence of linkage and association between the ROR2 gene and a gene controlling risk to non-syndromic cleft palate.
文摘Cleft lip with or without cleft palate(CP) is one of the most common congenital malformations. Ultrasonographers involved in the routine 20-wk ultrasound screening could encounter these malformations. The face and palate develop in a very characteristic way. For ultrasonographers involved in screening these patients it is crucial to have a thorough understanding of the embryology of the face. This could help them to make a more accurate diagnosis and save time during the ultrasound. Subsequently, the current postnatal classification will be discussed to facilitate the communication with the CP teams.
文摘The acoustic characteristics or the chinese vowels of 24 children with cleft palate and 10 normal control children were analyzed by computerized speech signal processing system (CSSPS),and the speech articulation was judged with Glossary of clert palate speech(GCPS).The listening judgement showed that the speech articulation was significantly different between the two groups(P<0.01).The objective quantitative measurement suggested that the formant pattern(FP)of vowels in children with cleft palate was different from that of normal control children except vowel[a](P< 0.05).The acoustic vowelgraph or the Chinese vowels which demonstrated directly the relationship of vocal space and speech perception was stated with the first formant frequence(F1)and the second formant frequence(F2).The authors conclude that the values or F1 and F2 point out the upward and backward tongue movement to close the clert, which reflects the vocal characteristics of trausmission of clert palate speech.
基金supported by the National Natural Science Foundation of China(60875014,60772039)
文摘An objective method, using a multi-band analysis technique, was proposed for analyzing plosive consonants in cleft palate speech. At first, the speech signal is decomposed in frequency domain using an auditory filter-bank. Then, the sample-based features, namely cumulative energy and its increment speed, in each band were computed. Finally, using principle component analysis, these features were fused into one combined feature vector for assessment. Since the algorithm is based on perceptual properties of human auditory ear using non-uniform and multi-band analysis, the improvements of the consistence between the proposed approach and subjective evaluation are obtained.
基金supported by the National Natural Science Foundation of China(No.81870747,82170916,81900984,and 82001030)the Fundamental Research Funds for the Central Universities(PKU2022XGK001)+2 种基金Natural Science Foundation of Beijing Municipality(7182184)Xi'an“Science and Technology+”Action Plan-Medical Research Project(20YXYJ0010[1])the Fundamental Research Funds for the Central Universities(xzy012020110).
文摘Orofacial clefts (OFCs) are the most common congenital craniofacial disorders, of which the etiology is closely related to rare coding variants. Filamin B (FLNB) is an actin-binding protein implicated in bone formation. FLNB mutations have been identified in several types of syndromic OFCs and previous studies suggest a role of FLNB in the onset of non-syndromic OFCs (NSOFCs). Here, we report two rare heterozygous variants (p.P441T and p.G565R) in FLNB in two unrelated hereditary families with NSOFCs. Bioinformatics analysis suggests that both variants may disrupt the function of FLNB. In mammalian cells, p.P441T and p.G565R variants are less potent to induce cell stretches than wild type FLNB, suggesting that they are loss-of-function mutations. Immunohistochemistry analysis demonstrates that FLNB is abundantly expressed during palatal development. Importantly, Flnb^(−/−) embryos display cleft palates and previously defined skeletal defects. Taken together, our findings reveal that FLNB is required for development of palates in mice and FLNB is a bona fide causal gene for NSOFCs in humans.
