Hereditary angioedema (HAE) is a rare,autosomal dominant inherited disorder with an incidence of approximately 1 in 50,000.Among its various tapes,HAE with normal C1 inhibitor levels (HAE-nC1-INH)is exceptionally rare...Hereditary angioedema (HAE) is a rare,autosomal dominant inherited disorder with an incidence of approximately 1 in 50,000.Among its various tapes,HAE with normal C1 inhibitor levels (HAE-nC1-INH)is exceptionally rare.^([1]) HAE symptoms include recurrent episodes of skin and mucosal edema that can occur anywhere in the body.^([1-4]) Laryngeal edema is life-threatening,as it can lead to airway obstruction and potentially fatal suffocation.^([1-3])Edema of the gastrointestinal mucosa may cause abdominal pain,vomiting,and symptoms that are often misdiagnosed as acute abdomen.^([1-4]) This study included four patients,including one with HAE-nC1-INH (genetic testing revealed a heterozygous mutation in the KNG1 gene (c.1404G>C:p.Q468H)) and three with HAE due to C1 inhibitor deficiency (HAE-C1-INH).This case series aims to increase knowledge of HAE by illustrating its diverse clinical presentations and emphasizing features that may prompt clinical suspicion and facilitate timely diagnosis.展开更多
China's Northern and Southern Dynasties period(3rd–6th centuries AD)marked a significant era of ethnic integration in northern China.However,previous ancient DNA studies have primarily focused on northern ethnic ...China's Northern and Southern Dynasties period(3rd–6th centuries AD)marked a significant era of ethnic integration in northern China.However,previous ancient DNA studies have primarily focused on northern ethnic groups,with limited research on the genetic formation of the hereditary elite family,especially considering their abundant archaeological record and clear material identity.In this study,we obtain the ancient genome of a hereditary elite family,Gao Bin(高宾,503 AD–572 AD),at 0.6473-fold coverage with 475,132 single-nucleotide polymorphisms(SNPs)on the 1240k panel.His mitochondrial haplogroup belongs to Z4 and Y-haplogroup to O1a1a2b-F2444∗.The genetic profile of Gao Bin is most similar to that of the northern Han Chinese.He can be modeled as deriving all his ancestry from Late Neolithic to Iron Age Yellow River farmers without influence from Northeast Asia,Korea,or the Mongolian Plateau.Our study sheds light on the genetic formation of hereditary elite families in the context of the Southern and Northern Dynasties ethnic integration.展开更多
Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower extre...Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower extremities.HSP is one significant cause of chronic neurodisability due to the lack of effective treatments and a wide range of onset ages from early childhood to 70 years.展开更多
BACKGROUND Postpartum pulmonary arterial hypertension(PAH)complicated with hereditary hemorrhagic telangiectasia(HHT)is a rare condition.Diagnosing and treating PAH in patients with HHT can be challenging.To the best ...BACKGROUND Postpartum pulmonary arterial hypertension(PAH)complicated with hereditary hemorrhagic telangiectasia(HHT)is a rare condition.Diagnosing and treating PAH in patients with HHT can be challenging.To the best of our knowledge,no previous reports have investigated the efficacy of pulmonary vasodilators in improving hemodynamics in postpartum patients with this disease.CASE SUMMARY In this paper,we report a postpartum case of HHT combined with PAH,pre-senting with worsening dyspnea.Genetic testing revealed that the patient carried a heterozygous variant of activin receptor-like kinase 1.The patient received various treatments,including diuretics,anticoagulants,sildenafil,macitentan,inhalation of nitric oxide,and iloprost.Changes in PaO2/FiO2,pulmonary artery systolic pressure as assessed by echocardiography,and N-terminus pro-brain natriuretic peptide levels suggested that,except for iloprost inhalation,the other treatments appeared to have limited efficacy.CONCLUSION To our knowledge,this is the first report on efficacy of pulmonary vasodilators in postpartum patients with HHT and PAH.展开更多
Hereditary multiple exostoses(HME)is an autosomal dominant bone disorder characterized by abnormal bone development.HME mostly involves the forearm,resulting in forearm deformities,limited functional activities,etc.Cu...Hereditary multiple exostoses(HME)is an autosomal dominant bone disorder characterized by abnormal bone development.HME mostly involves the forearm,resulting in forearm deformities,limited functional activities,etc.Currently,there are multiple surgical methods including tumor resection with or without ulnar osteotomy and lengthening,simple radial head resection and distal radial hemiepiphysiodesis,but the optimal treatment remains controversial.Ulnar lengthening serves as an effective surgical intervention for forearm deformities in HME patients.This review examines its surgical techniques,complications,and timing of the operation to guide clinical decision-making for improving function and cosmetic outcomes.展开更多
Hereditary spherocytosis(HS),a common inherited hemolytic anemia,is characterized by red blood cell membrane protein defects leading to chronic hemolysis.This condition significantly predisposes patients to gallstone ...Hereditary spherocytosis(HS),a common inherited hemolytic anemia,is characterized by red blood cell membrane protein defects leading to chronic hemolysis.This condition significantly predisposes patients to gallstone disease,including both gallbladder and bile duct stones,due to excessive bilirubin production from hemolysis.Gallstones in HS patients,primarily composed of bilirubin,can lead to complications such as cholecystitis,cholangitis,and obstructive jaundice.This review provides a comprehensive landscape of the pathophysiological mechanisms linking HS to gallstone formation,emphasizing the roles of hemolysis,bile composition,and genetic factors.It also discusses the clinical manifestations of gallstone disease in HS,including recurrent jaundice and biliary obstruction,and highlights the diagnostic value of imaging modalities such as ultrasonography and magnetic resonance cholangiopancreatography.Furthermore,current management strategies,including splenectomy,cholecystectomy,and endoscopic approaches for bile duct stones,are examined in the context of HS.By synthesizing existing knowledge,this review aims to provide insights into improving the diagnosis,prevention,and treatment of gallstone disease in patients with HS,while identifying gaps for future research.展开更多
Hereditary alpha tryptasemia was first described in 2016 and is the most common(up to 72%)cause of elevated serum basal tryptase(TPS).The clinical presentation of this condition,which is caused by copy number gains in...Hereditary alpha tryptasemia was first described in 2016 and is the most common(up to 72%)cause of elevated serum basal tryptase(TPS).The clinical presentation of this condition,which is caused by copy number gains in the TPSAB1 gene encoding serumαTPS,is variable for each patient.Some patients are asymptomatic,whereas in others,especially those with increased mast cell activation,it has been associated with a higher risk of anaphylaxis.Better characterization of this entity is important to identify atrisk patients and to develop new treatment strategies.This review provided an overview of hereditary alpha tryptasemia and increased awareness of this condition by discussing the current information in the literature.展开更多
Hearing loss is one of the most prevalent sensory disorders affecting the human nervous system.Liquid–liquid phase separation(LLPS)is a physiological process that facilitates the reversible and dynamic assembly of bi...Hearing loss is one of the most prevalent sensory disorders affecting the human nervous system.Liquid–liquid phase separation(LLPS)is a physiological process that facilitates the reversible and dynamic assembly of biomolecular condensates.Increasing evidence suggests that LLPS plays a significant role in the pathogenesis of hereditary hearing loss.Nevertheless,there is a conspicuous lack of systematic investigations exploring the impact of LLPS abnormalities on the etiology of hereditary hearing loss.In this review,we examine the mechanisms by which dysfunctions in LLPS contribute to hereditary hearing loss,specifically focusing on its effects on mechanoelectrical transduction in hair bundles,transcriptional regulation,post-transcriptional modifications,the actin cytoskeleton,ion homeostasis within the inner ear,and energy and redox homeostasis.Furthermore,we evaluate the considerable potential of targeting LLPS as a therapeutic approach for hearing loss and propose innovative perspectives on LLPS that may guide future research initiatives in the field of auditory disorders.展开更多
In this editorial,I commented on the paper by Lin et al,published in this issue of the World Journal of Gastrointestinal Oncology.The work aimed at analysing the clinicopathologic characteristics and prognosis of sync...In this editorial,I commented on the paper by Lin et al,published in this issue of the World Journal of Gastrointestinal Oncology.The work aimed at analysing the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with dual primary gastric and colorectal cancer(CRC).The authors concluded the necessity for regular surveillance for metachronous cancer during postoperative follow-up and reported the prognosis is influenced by the gastric cancer(GC)stage rather than the CRC stage.Although surveillance was recommended in the conclusion,the authors did not explore this area in their study and did not include tests used for such surveillance.This editorial focuses on the most characterized gastrointestinal cancer susceptibility syndromes concerning dual gastric and CRCs.These include hereditary diffuse GC,familial adenomatous polyposis,hereditary nonpolyposis colon cancer,Lynch syndrome,and three major hamartomatous polyposis syndromes associated with CRC and GC,namely Peutz-Jeghers syndrome,juvenile polyposis syndrome,and PTEN hamartoma syndrome.Careful assessment of these syndromes/conditions,including inheritance,risk of gastric and colorectal or other cancer development,genetic mutations and recommended genetic investigations,is crucial for optimum management of these patients.展开更多
[Objective] This study aimed to investigate the hereditary stability of sFat-1 transgenic pigs and the differences in disease susceptivity between sFat-1 transgenic pigs and non-transgenic pigs. [Method] The integrati...[Objective] This study aimed to investigate the hereditary stability of sFat-1 transgenic pigs and the differences in disease susceptivity between sFat-1 transgenic pigs and non-transgenic pigs. [Method] The integration of sFat-1 gene in pigs was detected by PCR; the infection of transgenic pig to pseudorabies, leptospirosis, swine dysentery, brucellosis, Mycobacterium tuberculosis, rotavirus and mycoplasma hyopneumoniae was detected by using ELISA and PCR. [Result] The positive ratio of F3 generation sFat-1 transgenic pigs was 18.5%; the susceptivity of positive sFat- 1 transgenic and negative pigs to seven infectious diseases showed no significant difference. [Conclusion] Exogenous gene in sFat-1 transgenic pigs can not be stably inherited. The overall physical condition of positive transgenic and negative pigs was similar.展开更多
The term Hereditary Non-Polyposis Colorectal Cancer （HNPCC） is a poor descriptor of the syndrome described by Lynch. Over the last decade, the term has been applied to heterogeneous groups of families meeting limite...The term Hereditary Non-Polyposis Colorectal Cancer （HNPCC） is a poor descriptor of the syndrome described by Lynch. Over the last decade, the term has been applied to heterogeneous groups of families meeting limited clinical criteria, for example the Amsterdam criteria. It is now apparent that not all Amsterdam criteria-positive families have the Lynch syndrome. The term HNPCC has also been applied to clinical scenarios in which CRCs with DNA microsateUite instability are diagnosed but in which there is no vertical transmission of an altered DNA mismatch repair （MMR） gene. A term that has multiple, mutually incompatible meanings is highly problematic, particularly when it may influence the management of an individual family. The Lynch syndrome is best understood as a hereditary predisposition to malignancy that is explained by a germline mutation in a DNA MMR gene. The diagnosis does not depend in an absolute sense on any particular family pedigree structure or age of onset of malignancy. Families with a strong family history of colorectal cancer that do not have Lynch syndrome have been grouped as ‘Familial Colorectal Cancer Type-X＇. The first step in characterizing these cancer families is to distinguish them from Lynch syndrome. The term HNPCC no longer serves any useful purpose and should be phased out.展开更多
AIM： To detect microsatellite instability （MSI） in patients with hereditary nonpolyposis colorectal cancer or ordinary hereditary colorectal cancer and to provide criteria for screening the kindreds with hereditary...AIM： To detect microsatellite instability （MSI） in patients with hereditary nonpolyposis colorectal cancer or ordinary hereditary colorectal cancer and to provide criteria for screening the kindreds with hereditary nonpolyposis colorectal cancer at molecular level.METHODS： MSI was detected in the specimens from 20 cases with HNPCC, 20 cases with ordinary hereditary colorectal cancer and 20 cases with sporadic colorectal cancer by means of polymerase chain reaction-single strand conformation polymorphism. RESULTS： The positive rate of MSI was 85% （17/20） in HNPCC group, 40% （8/20） in ordinary hereditary colorectal cancer group and 10% （2/20） in the sporadic colorectal cancer group respectively. The differences were significant. The mean ages of the three groups were 43.6, 52.2, and 61.8 years respectively, which increased gradually. The incidence of right hemicolon cancer was 64.7%, 37.5%, and 0% respectively, which decreased gradually and had significant difference. The expression ratio of BAT26 and BAT25 was 94.1% respectively, which was highest in the 5 gene sites studied. The incidence of poorly differentiated adenocarcinoma was 70.6% in HNPCC group among high frequency microsatellite instability （MSI-H）, which was higher than the other two groups, which had 50% and 50% respectively. CONCLUSION： The incidence of MSI-H is higher in HNPCC group. The detection of MSI is simple and economical and has high correlation with the clinicopathologic feature of HNPCC and can be used as a screening method to detect the germ line mutation of the mismatch repair gene.展开更多
A novel mutation of vascular endothelial growth factor receptor gene （VEGFR-3）, was identified in a four-generation Chinese family with hereditary lymphedema type I （HL-I）. Genetic linkage analysis was performed o...A novel mutation of vascular endothelial growth factor receptor gene （VEGFR-3）, was identified in a four-generation Chinese family with hereditary lymphedema type I （HL-I）. Genetic linkage analysis was performed on the known genetic locus for HL-I with a panel of polymorphic markers, and then mutations were screened out by direct sequencing. By genotyping, the family showed the linkage to HL-I locus on 5q35.3. Mutation screening analysis of the exons encoding the intracellular kinase domains of VEGFR-3, revealed a novel missense mutation D1055V. This mutation cosegregated with the disease phenotype in the family and was not found in 100 normal controls. This finding has expanded the spectrum of the VEGFR-3 gene mutations causing HL-I, and will be useful for further genetic consultation and genetic diagnosis.展开更多
AIM:To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome(HHCS). METHODS:Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position+40 in the ...AIM:To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome(HHCS). METHODS:Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position+40 in the L-ferritin gene,were recruited to undergo serum hepcidin and prohepcidin measurements using radioimmunoassay and enzyme linked immunoassay,respectively,and measurements were compared with levels in serum from 25 healthy volunteers(14 females),mean age 36±11.9 years.RESULTS:The serum hepcidin and prohepcidin levels in patients with HHCS were 19.1±18.6 and 187± 120.9 ng/mL,respectively.Serum ferritin was 1716.3± 376μg/L.Liver biopsy in one patient did not show any evidence of iron overload.Serum hepcidin and prohepcidin values in healthy controls(HCs)were 15.30±15.71 and 236.88±83.68 ng/mL,respectively,while serum ferritin was 110±128.08μg/L.There was no statistical difference in serum hepcidin level between the two cohorts(19.1±18.6 ng/mL vs 15.30±15.71 ng/mL,P= 0.612)using two-tailed t-test. CONCLUSION:Serum hepcidin levels in HHCS patients is similar to that in HCs.Our study suggests that circulating ferritin is not a factor influencing hepcidin synthesis and does not have a role in the iron-sensing mechanism in hepatocytes.展开更多
AIM: To describe systematically the clinical characteristics and phenotype of HNPCC families and the prevalence of HNPCC in the general population of CRC patients in China. METHODS: HNPCC kindreds and CRC patients wer...AIM: To describe systematically the clinical characteristics and phenotype of HNPCC families and the prevalence of HNPCC in the general population of CRC patients in China. METHODS: HNPCC kindreds and CRC patients were from two sources. One was that we consecutively investigated kindreds and patients by ourselves. And the other was the published Chinese and foreign literature related to Chinese HNPCC syndrome. There were 142 HNPCC families fulfilling AC I and/or AC II including 57 families with detailed data, and 3874 general primary CRC patients in all. All statistical tests were two-sided. RESULTS: In AC I families, the number of Lynch syndrome I and II families were 25 (47.2%) and 28 (52.8%) respectively. There were 215 patients (82.4%) with CRC, 67 patients (25.7%) with extracolonic cancer and 50 patients (19.2%) with multiple primary cancers. In all CRC patients, multiple primary CRC were in 41 patients (19.1%), and the first-CRC was right-sided colorectal cancer in 143 patients (66.5%) and rectal cancer in 44 patients (20.5%). 8.8% and 19.2% of the first cancer were CRC and extracolonic cancers. Among those patients whose first cancer was CRC, 66.8% and 19.9% were right-sided colorectal cancer and rectal cancer, respectively. The similar results were found in AC II families. Normal distribution was only found in the distribution of the age of diagnosis of the first cancer in both AC I families (coefficient of skewness: u = 0.81, 0.20<0.40<P<0.50; coefficient of kurtosis: u = 1.13, 0.20<P<0.40,α=0.20) and AC II families (coefficient of skewness: u=0.63, P>0.5> 0.20; coefficient of kurtosis: u = 0.84, 0.20<0.40<P<0.50, α=0.20), but not found in the distribution of the age of diagnosis of the first CRC. When patients with HNPCC-associated cancer suffered from the first malignant tumor in HNPCC families diagnosed by AC I and AC II, the mean age and median age were 45.1±12.7 years and 44.0 years, 45.2±12.7 years and 44.5 years, respectively. The median age of diagnosis of the first tumor of the patients in the later generation was younger than that in the previous generation. Many extracolonic cancers were found to be associated with HNPCC syndrome. Gastric cancer was the most frequent extracolonic cancer followed by endometrial cancer and hepatocarcinoma. In general population of CRC patients, the prevalence of HNPCC diagnosed by AC I and AC II were 1.3% and 2.2%, respectively. CONCLUSION: The clinical phenotype and prevalence of Chinese HNPCC syndrome are similar to those of Europeans and Americans. Gastric cancer is the most common extracolonic malignant tumor. The age of diagnosis of the first malignant tumor tends to be increasingly younger in patients with HNPCC-related tumors.展开更多
The Stem Cell Ophthalmology Treatment Study （SCOTS） is currently the largest-scale stem cell ophthal- mology trial registered at ClinicalTrials.gov （identifier： NCT01920867）. SCOTS utilizes autologous bone marrow...The Stem Cell Ophthalmology Treatment Study （SCOTS） is currently the largest-scale stem cell ophthal- mology trial registered at ClinicalTrials.gov （identifier： NCT01920867）. SCOTS utilizes autologous bone marrow-derived stem cells （BMSCs） to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber＇s hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study （ETDRS） of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting fingers to 20/100. Visual field improvements were noted. Macular and optic nerve head nerve fiber layer typically thickened. No serious complications were seen. The increases in visual acuity obtained in our study were encouraging and suggest that the use of autolo- gous BMSCs as provided in SCOTS for ophthalmologic mitochondrial diseases including Leber＇s hereditary optic neuropathy may be a viable treatment option.展开更多
AIM: To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families. METHODS: Thirty-six kindreds ...AIM: To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families. METHODS: Thirty-six kindreds were tested for mutations using conformation sensitive gel electrophoreses, direct sequencing and also screening for genomic rearrangements applying multiplex ligation-dependent probe amplifi cation (MLPA). RESULTS: Eighteen germline mutations (50%) were identifi ed, 9 in MLH1 and 9 in MSH2. Sixteen of these sequence alterations were considered pathogenic, the remaining two were non-conservative missense alterations occurring at highly conserved functional motifs. The majority of the defi nite pathogenic mutations (81%, 13/16) were found in families fulfilling the stringent Amsterdam Ⅰ/Ⅱ criteria, including three rearrangements revealed by MLPA (two in MSH2 and one in MLH1). However, in three out of sixteen HNPCC-suspected families (19%), a disease-causing alteration could be revealed. Furthermore, nine mutations described here are novel, and none of the sequence changes were found in more than one family.CONCLUSION: Our study describes for the f irst time the prevalence and spectrum of germline mismatch repair gene mutations in Hungarian HNPCC and suspected-HNPCC families. The results presented here suggest that clinical selection criteria should be relaxed and detection of genomic rearrangements should be included in genetic screening in this population.展开更多
Hereditary non-polyposis colorectal cancer(HNPCC) was previously synonymous with Lynch syndrome; however,identification of the role of germline mutations in the DNA mismatch repair(MMR) genes has made it possible to d...Hereditary non-polyposis colorectal cancer(HNPCC) was previously synonymous with Lynch syndrome; however,identification of the role of germline mutations in the DNA mismatch repair(MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer(CRC). Broadly,HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability(MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome(germline MMR mutation),Lynch-like syndrome(biallelic somatic MMR mutations),constitutional MMR deficiency syndrome(biallelic germline MMR mutations),and sporadic MSI CRC(somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions,others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management.展开更多
AIM： To analyze the frequency of hereditary non-polyposis colorectal cancer （HNPCC） in Chinese colorectal cancer （CRC） patients, and to discuss the value of microsatellite instability （MSI） and/or immunohistoch...AIM： To analyze the frequency of hereditary non-polyposis colorectal cancer （HNPCC） in Chinese colorectal cancer （CRC） patients, and to discuss the value of microsatellite instability （MSI） and/or immunohistochemistry （IHC） for MSH2/MLH1 protein analysis as pre-screening tests in China. METHODS： The Amsterdam criteria Ⅰ and Ⅱ （clinical diagnosis） and/or germline hMLHI/hMSH2 mutations （genetic diagnosis） were used to classify HNPCC families. Genetic tests, including microsatellite instability, immunohistochemistry for MSH2/MLH1 proteins and hMSH2/hMLH1 genes, were performed in each proband. RESULTS： From July 2000 to June 2004, 1988 patients with colorectal cancer were analysed and 114 CRC patients （5.7%） from 48 families were categorized as having HNPCC, including 76 from 26 families diagnosed clinically and 38 from the other 22 families diagnosed genetically. The sensitivity and specificity of high MSI and IHC for predicting mutations were 100% and 54%, and 79% and 77%, respectively. CONCLUSION： The frequency of HNPCC is approximately 10% among all Chinese CRC cases. The MSI and IHC detections for hMSH2/hMLH1 proteins are reliable prescreening tests for hMLHI/hMSH2 germline mutations in families suspected of having HNPCC.展开更多
AIM:To study the germline mutation of hPMS2 gene in 26 unrelated Chinese hereditary nonpolyposis colorectal cancer(HNPCC)probands and to fulfill the screening strategy for HNPCC in Chinese.METHODS:Genomic DNA was extr...AIM:To study the germline mutation of hPMS2 gene in 26 unrelated Chinese hereditary nonpolyposis colorectal cancer(HNPCC)probands and to fulfill the screening strategy for HNPCC in Chinese.METHODS:Genomic DNA was extracted from the peripheral blood.To avoid the interference of pseudogene in detection of the remaining 11 exons(exon 1-5,9,11-15),long-range polymerase chain reaction(PCR)was conducted to amplify the complete coding region of hPMS2 gene firstly.Then 1/8 of the PCR productswere used as template to amplify the individual exon respectively and DNA sequencing was done.Direct DNA sequencing of the conventional PCR products of exon 6,7,8 and 10 of hPMS2 gene was performed.The same analysis was made in 130 healthy persons without family histories of HNPCC to further investigate the pathological effects of the detected missense mutation.RESULTS:One HNPCC proband fulf illed Bethesda guidelines and was found to carry the germline mutation of hPMS2 gene,which has not been reported in Chinese HNPCC families.It was a missense mutation at c.1532C>T of exon 11.It was detected in three controls as well with an occurrence rate of 2.3%(3/130).Since it could not be found in the PMS2-single nucleotide polymorphism(SNP)database,this missense mutation is a new SNP unreported up to date.Meanwhile,260 reported SNPs of hPMS2 gene were detected in the 26 HNPCC probands.The 2nd and 5th exons were probably the hot SNP regions of hPMS2 gene in Chinese HNPCC families involving 53.1%of all reported SNP.CONCLUSION:The germline mutation of hPMS2 gene may be rare in Chinese HNPCC families.The 2nd and 5th exons are hot SNP regions of hPMS2 gene.展开更多
基金supported by the National Social Science Fund of China (19VJX168)。
文摘Hereditary angioedema (HAE) is a rare,autosomal dominant inherited disorder with an incidence of approximately 1 in 50,000.Among its various tapes,HAE with normal C1 inhibitor levels (HAE-nC1-INH)is exceptionally rare.^([1]) HAE symptoms include recurrent episodes of skin and mucosal edema that can occur anywhere in the body.^([1-4]) Laryngeal edema is life-threatening,as it can lead to airway obstruction and potentially fatal suffocation.^([1-3])Edema of the gastrointestinal mucosa may cause abdominal pain,vomiting,and symptoms that are often misdiagnosed as acute abdomen.^([1-4]) This study included four patients,including one with HAE-nC1-INH (genetic testing revealed a heterozygous mutation in the KNG1 gene (c.1404G>C:p.Q468H)) and three with HAE due to C1 inhibitor deficiency (HAE-C1-INH).This case series aims to increase knowledge of HAE by illustrating its diverse clinical presentations and emphasizing features that may prompt clinical suspicion and facilitate timely diagnosis.
基金funded by the National Natural Science Foundation of China(32070576,31801040,and 32270667)Lantai Young Scholars Program of Chinese History Institute(2022LTQN602)+11 种基金the National Social Science Fund of China(19VJX074 and 21CKG022)Priority Research Program of the Chinese Academy of Sciences:Pan-Third Pole Environment Study for a Green Silk Road(Pan-TPE)(XDA2004010101)the National Key Research and Development Program(2023YFC3303701-02)the Natural Science Foundation of Fujian Province of China(2023J06013)the Science and Technology Commission of Shanghai Municipality(18490750300)the National Key Research and Development Program(2020YFE0201600)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)the Major Project of National Social Science Foundation of China granted to C.C.W.(21&ZD285),S.W.(20&ZD212),and D.L.(21&ZD237)Major Special Project of Philosophy and Social Sciences Research of the Ministry of Education(2022JZDZ023)Open Research Fund of State Key Laboratory of Genetic Engineering at Fudan University(SKLGE-2310)Open Research Fund of Forensic Genetics Key Laboratory of the Ministry of Public Security(2023FGKFKT07)European Research Council(ERC)grant(ERC-2019-ADG-883700-TRAM).
文摘China's Northern and Southern Dynasties period(3rd–6th centuries AD)marked a significant era of ethnic integration in northern China.However,previous ancient DNA studies have primarily focused on northern ethnic groups,with limited research on the genetic formation of the hereditary elite family,especially considering their abundant archaeological record and clear material identity.In this study,we obtain the ancient genome of a hereditary elite family,Gao Bin(高宾,503 AD–572 AD),at 0.6473-fold coverage with 475,132 single-nucleotide polymorphisms(SNPs)on the 1240k panel.His mitochondrial haplogroup belongs to Z4 and Y-haplogroup to O1a1a2b-F2444∗.The genetic profile of Gao Bin is most similar to that of the northern Han Chinese.He can be modeled as deriving all his ancestry from Late Neolithic to Iron Age Yellow River farmers without influence from Northeast Asia,Korea,or the Mongolian Plateau.Our study sheds light on the genetic formation of hereditary elite families in the context of the Southern and Northern Dynasties ethnic integration.
基金supported by the NIH grant(RO1 NS118066)the Blazer Foundation(to XJL)。
文摘Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower extremities.HSP is one significant cause of chronic neurodisability due to the lack of effective treatments and a wide range of onset ages from early childhood to 70 years.
基金Supported by the Shanghai Sailing Program,No.21YF1440300 and No.22YF1407700and the National Natural Science Foundation of China,No.82200061.
文摘BACKGROUND Postpartum pulmonary arterial hypertension(PAH)complicated with hereditary hemorrhagic telangiectasia(HHT)is a rare condition.Diagnosing and treating PAH in patients with HHT can be challenging.To the best of our knowledge,no previous reports have investigated the efficacy of pulmonary vasodilators in improving hemodynamics in postpartum patients with this disease.CASE SUMMARY In this paper,we report a postpartum case of HHT combined with PAH,pre-senting with worsening dyspnea.Genetic testing revealed that the patient carried a heterozygous variant of activin receptor-like kinase 1.The patient received various treatments,including diuretics,anticoagulants,sildenafil,macitentan,inhalation of nitric oxide,and iloprost.Changes in PaO2/FiO2,pulmonary artery systolic pressure as assessed by echocardiography,and N-terminus pro-brain natriuretic peptide levels suggested that,except for iloprost inhalation,the other treatments appeared to have limited efficacy.CONCLUSION To our knowledge,this is the first report on efficacy of pulmonary vasodilators in postpartum patients with HHT and PAH.
文摘Hereditary multiple exostoses(HME)is an autosomal dominant bone disorder characterized by abnormal bone development.HME mostly involves the forearm,resulting in forearm deformities,limited functional activities,etc.Currently,there are multiple surgical methods including tumor resection with or without ulnar osteotomy and lengthening,simple radial head resection and distal radial hemiepiphysiodesis,but the optimal treatment remains controversial.Ulnar lengthening serves as an effective surgical intervention for forearm deformities in HME patients.This review examines its surgical techniques,complications,and timing of the operation to guide clinical decision-making for improving function and cosmetic outcomes.
文摘Hereditary spherocytosis(HS),a common inherited hemolytic anemia,is characterized by red blood cell membrane protein defects leading to chronic hemolysis.This condition significantly predisposes patients to gallstone disease,including both gallbladder and bile duct stones,due to excessive bilirubin production from hemolysis.Gallstones in HS patients,primarily composed of bilirubin,can lead to complications such as cholecystitis,cholangitis,and obstructive jaundice.This review provides a comprehensive landscape of the pathophysiological mechanisms linking HS to gallstone formation,emphasizing the roles of hemolysis,bile composition,and genetic factors.It also discusses the clinical manifestations of gallstone disease in HS,including recurrent jaundice and biliary obstruction,and highlights the diagnostic value of imaging modalities such as ultrasonography and magnetic resonance cholangiopancreatography.Furthermore,current management strategies,including splenectomy,cholecystectomy,and endoscopic approaches for bile duct stones,are examined in the context of HS.By synthesizing existing knowledge,this review aims to provide insights into improving the diagnosis,prevention,and treatment of gallstone disease in patients with HS,while identifying gaps for future research.
文摘Hereditary alpha tryptasemia was first described in 2016 and is the most common(up to 72%)cause of elevated serum basal tryptase(TPS).The clinical presentation of this condition,which is caused by copy number gains in the TPSAB1 gene encoding serumαTPS,is variable for each patient.Some patients are asymptomatic,whereas in others,especially those with increased mast cell activation,it has been associated with a higher risk of anaphylaxis.Better characterization of this entity is important to identify atrisk patients and to develop new treatment strategies.This review provided an overview of hereditary alpha tryptasemia and increased awareness of this condition by discussing the current information in the literature.
基金supported by the National Natural Science Foundation of China(82430035)the Foundation for Innovative Research Groups of Hubei Province(2023AFA038)+1 种基金the National Key Research and Development Program of China(2021YFF0702303,2024YFC2511101,and 2023YFE0203200)the Fundamental Research Funds for the Central Universities(2024BRA019).
文摘Hearing loss is one of the most prevalent sensory disorders affecting the human nervous system.Liquid–liquid phase separation(LLPS)is a physiological process that facilitates the reversible and dynamic assembly of biomolecular condensates.Increasing evidence suggests that LLPS plays a significant role in the pathogenesis of hereditary hearing loss.Nevertheless,there is a conspicuous lack of systematic investigations exploring the impact of LLPS abnormalities on the etiology of hereditary hearing loss.In this review,we examine the mechanisms by which dysfunctions in LLPS contribute to hereditary hearing loss,specifically focusing on its effects on mechanoelectrical transduction in hair bundles,transcriptional regulation,post-transcriptional modifications,the actin cytoskeleton,ion homeostasis within the inner ear,and energy and redox homeostasis.Furthermore,we evaluate the considerable potential of targeting LLPS as a therapeutic approach for hearing loss and propose innovative perspectives on LLPS that may guide future research initiatives in the field of auditory disorders.
文摘In this editorial,I commented on the paper by Lin et al,published in this issue of the World Journal of Gastrointestinal Oncology.The work aimed at analysing the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with dual primary gastric and colorectal cancer(CRC).The authors concluded the necessity for regular surveillance for metachronous cancer during postoperative follow-up and reported the prognosis is influenced by the gastric cancer(GC)stage rather than the CRC stage.Although surveillance was recommended in the conclusion,the authors did not explore this area in their study and did not include tests used for such surveillance.This editorial focuses on the most characterized gastrointestinal cancer susceptibility syndromes concerning dual gastric and CRCs.These include hereditary diffuse GC,familial adenomatous polyposis,hereditary nonpolyposis colon cancer,Lynch syndrome,and three major hamartomatous polyposis syndromes associated with CRC and GC,namely Peutz-Jeghers syndrome,juvenile polyposis syndrome,and PTEN hamartoma syndrome.Careful assessment of these syndromes/conditions,including inheritance,risk of gastric and colorectal or other cancer development,genetic mutations and recommended genetic investigations,is crucial for optimum management of these patients.
基金Supported by National Major Program of Genetically Modified Organism for New Species Cultivation of China(2011ZX08011-004)Project from Hubei Agricultural Science and Technology Innovation Center(2011-620-001-003)~~
文摘[Objective] This study aimed to investigate the hereditary stability of sFat-1 transgenic pigs and the differences in disease susceptivity between sFat-1 transgenic pigs and non-transgenic pigs. [Method] The integration of sFat-1 gene in pigs was detected by PCR; the infection of transgenic pig to pseudorabies, leptospirosis, swine dysentery, brucellosis, Mycobacterium tuberculosis, rotavirus and mycoplasma hyopneumoniae was detected by using ELISA and PCR. [Result] The positive ratio of F3 generation sFat-1 transgenic pigs was 18.5%; the susceptivity of positive sFat- 1 transgenic and negative pigs to seven infectious diseases showed no significant difference. [Conclusion] Exogenous gene in sFat-1 transgenic pigs can not be stably inherited. The overall physical condition of positive transgenic and negative pigs was similar.
文摘The term Hereditary Non-Polyposis Colorectal Cancer （HNPCC） is a poor descriptor of the syndrome described by Lynch. Over the last decade, the term has been applied to heterogeneous groups of families meeting limited clinical criteria, for example the Amsterdam criteria. It is now apparent that not all Amsterdam criteria-positive families have the Lynch syndrome. The term HNPCC has also been applied to clinical scenarios in which CRCs with DNA microsateUite instability are diagnosed but in which there is no vertical transmission of an altered DNA mismatch repair （MMR） gene. A term that has multiple, mutually incompatible meanings is highly problematic, particularly when it may influence the management of an individual family. The Lynch syndrome is best understood as a hereditary predisposition to malignancy that is explained by a germline mutation in a DNA MMR gene. The diagnosis does not depend in an absolute sense on any particular family pedigree structure or age of onset of malignancy. Families with a strong family history of colorectal cancer that do not have Lynch syndrome have been grouped as ‘Familial Colorectal Cancer Type-X＇. The first step in characterizing these cancer families is to distinguish them from Lynch syndrome. The term HNPCC no longer serves any useful purpose and should be phased out.
文摘AIM： To detect microsatellite instability （MSI） in patients with hereditary nonpolyposis colorectal cancer or ordinary hereditary colorectal cancer and to provide criteria for screening the kindreds with hereditary nonpolyposis colorectal cancer at molecular level.METHODS： MSI was detected in the specimens from 20 cases with HNPCC, 20 cases with ordinary hereditary colorectal cancer and 20 cases with sporadic colorectal cancer by means of polymerase chain reaction-single strand conformation polymorphism. RESULTS： The positive rate of MSI was 85% （17/20） in HNPCC group, 40% （8/20） in ordinary hereditary colorectal cancer group and 10% （2/20） in the sporadic colorectal cancer group respectively. The differences were significant. The mean ages of the three groups were 43.6, 52.2, and 61.8 years respectively, which increased gradually. The incidence of right hemicolon cancer was 64.7%, 37.5%, and 0% respectively, which decreased gradually and had significant difference. The expression ratio of BAT26 and BAT25 was 94.1% respectively, which was highest in the 5 gene sites studied. The incidence of poorly differentiated adenocarcinoma was 70.6% in HNPCC group among high frequency microsatellite instability （MSI-H）, which was higher than the other two groups, which had 50% and 50% respectively. CONCLUSION： The incidence of MSI-H is higher in HNPCC group. The detection of MSI is simple and economical and has high correlation with the clinicopathologic feature of HNPCC and can be used as a screening method to detect the germ line mutation of the mismatch repair gene.
文摘A novel mutation of vascular endothelial growth factor receptor gene （VEGFR-3）, was identified in a four-generation Chinese family with hereditary lymphedema type I （HL-I）. Genetic linkage analysis was performed on the known genetic locus for HL-I with a panel of polymorphic markers, and then mutations were screened out by direct sequencing. By genotyping, the family showed the linkage to HL-I locus on 5q35.3. Mutation screening analysis of the exons encoding the intracellular kinase domains of VEGFR-3, revealed a novel missense mutation D1055V. This mutation cosegregated with the disease phenotype in the family and was not found in 100 normal controls. This finding has expanded the spectrum of the VEGFR-3 gene mutations causing HL-I, and will be useful for further genetic consultation and genetic diagnosis.
基金Supported by Research and Development Department,Ealing Hospital NHS Trust,Uxbridge Road,Southall,London,UB13HW,United Kingdom
文摘AIM:To study the role of hepcidin in hereditary hyperferritinemia cataract syndrome(HHCS). METHODS:Six patients from two families with HHCS, confirmed by genetic analysis showing A to G mutation at position+40 in the L-ferritin gene,were recruited to undergo serum hepcidin and prohepcidin measurements using radioimmunoassay and enzyme linked immunoassay,respectively,and measurements were compared with levels in serum from 25 healthy volunteers(14 females),mean age 36±11.9 years.RESULTS:The serum hepcidin and prohepcidin levels in patients with HHCS were 19.1±18.6 and 187± 120.9 ng/mL,respectively.Serum ferritin was 1716.3± 376μg/L.Liver biopsy in one patient did not show any evidence of iron overload.Serum hepcidin and prohepcidin values in healthy controls(HCs)were 15.30±15.71 and 236.88±83.68 ng/mL,respectively,while serum ferritin was 110±128.08μg/L.There was no statistical difference in serum hepcidin level between the two cohorts(19.1±18.6 ng/mL vs 15.30±15.71 ng/mL,P= 0.612)using two-tailed t-test. CONCLUSION:Serum hepcidin levels in HHCS patients is similar to that in HCs.Our study suggests that circulating ferritin is not a factor influencing hepcidin synthesis and does not have a role in the iron-sensing mechanism in hepatocytes.
文摘AIM: To describe systematically the clinical characteristics and phenotype of HNPCC families and the prevalence of HNPCC in the general population of CRC patients in China. METHODS: HNPCC kindreds and CRC patients were from two sources. One was that we consecutively investigated kindreds and patients by ourselves. And the other was the published Chinese and foreign literature related to Chinese HNPCC syndrome. There were 142 HNPCC families fulfilling AC I and/or AC II including 57 families with detailed data, and 3874 general primary CRC patients in all. All statistical tests were two-sided. RESULTS: In AC I families, the number of Lynch syndrome I and II families were 25 (47.2%) and 28 (52.8%) respectively. There were 215 patients (82.4%) with CRC, 67 patients (25.7%) with extracolonic cancer and 50 patients (19.2%) with multiple primary cancers. In all CRC patients, multiple primary CRC were in 41 patients (19.1%), and the first-CRC was right-sided colorectal cancer in 143 patients (66.5%) and rectal cancer in 44 patients (20.5%). 8.8% and 19.2% of the first cancer were CRC and extracolonic cancers. Among those patients whose first cancer was CRC, 66.8% and 19.9% were right-sided colorectal cancer and rectal cancer, respectively. The similar results were found in AC II families. Normal distribution was only found in the distribution of the age of diagnosis of the first cancer in both AC I families (coefficient of skewness: u = 0.81, 0.20<0.40<P<0.50; coefficient of kurtosis: u = 1.13, 0.20<P<0.40,α=0.20) and AC II families (coefficient of skewness: u=0.63, P>0.5> 0.20; coefficient of kurtosis: u = 0.84, 0.20<0.40<P<0.50, α=0.20), but not found in the distribution of the age of diagnosis of the first CRC. When patients with HNPCC-associated cancer suffered from the first malignant tumor in HNPCC families diagnosed by AC I and AC II, the mean age and median age were 45.1±12.7 years and 44.0 years, 45.2±12.7 years and 44.5 years, respectively. The median age of diagnosis of the first tumor of the patients in the later generation was younger than that in the previous generation. Many extracolonic cancers were found to be associated with HNPCC syndrome. Gastric cancer was the most frequent extracolonic cancer followed by endometrial cancer and hepatocarcinoma. In general population of CRC patients, the prevalence of HNPCC diagnosed by AC I and AC II were 1.3% and 2.2%, respectively. CONCLUSION: The clinical phenotype and prevalence of Chinese HNPCC syndrome are similar to those of Europeans and Americans. Gastric cancer is the most common extracolonic malignant tumor. The age of diagnosis of the first malignant tumor tends to be increasingly younger in patients with HNPCC-related tumors.
文摘The Stem Cell Ophthalmology Treatment Study （SCOTS） is currently the largest-scale stem cell ophthal- mology trial registered at ClinicalTrials.gov （identifier： NCT01920867）. SCOTS utilizes autologous bone marrow-derived stem cells （BMSCs） to treat optic nerve and retinal diseases. Treatment approaches include a combination of retrobulbar, subtenon, intravitreal, intra-optic nerve, subretinal, and intravenous injection of autologous BMSCs according to the nature of the disease, the degree of visual loss, and any risk factors related to the treatments. Patients with Leber＇s hereditary optic neuropathy had visual acuity gains on the Early Treatment Diabetic Retinopathy Study （ETDRS） of up to 35 letters and Snellen acuity improvements from hand motion to 20/200 and from counting fingers to 20/100. Visual field improvements were noted. Macular and optic nerve head nerve fiber layer typically thickened. No serious complications were seen. The increases in visual acuity obtained in our study were encouraging and suggest that the use of autolo- gous BMSCs as provided in SCOTS for ophthalmologic mitochondrial diseases including Leber＇s hereditary optic neuropathy may be a viable treatment option.
基金Supported by the Hungarian Research Grants OTKA T-046570, NKFPI-00024/2005 and ETT 397/2006
文摘AIM: To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families. METHODS: Thirty-six kindreds were tested for mutations using conformation sensitive gel electrophoreses, direct sequencing and also screening for genomic rearrangements applying multiplex ligation-dependent probe amplifi cation (MLPA). RESULTS: Eighteen germline mutations (50%) were identifi ed, 9 in MLH1 and 9 in MSH2. Sixteen of these sequence alterations were considered pathogenic, the remaining two were non-conservative missense alterations occurring at highly conserved functional motifs. The majority of the defi nite pathogenic mutations (81%, 13/16) were found in families fulfilling the stringent Amsterdam Ⅰ/Ⅱ criteria, including three rearrangements revealed by MLPA (two in MSH2 and one in MLH1). However, in three out of sixteen HNPCC-suspected families (19%), a disease-causing alteration could be revealed. Furthermore, nine mutations described here are novel, and none of the sequence changes were found in more than one family.CONCLUSION: Our study describes for the f irst time the prevalence and spectrum of germline mismatch repair gene mutations in Hungarian HNPCC and suspected-HNPCC families. The results presented here suggest that clinical selection criteria should be relaxed and detection of genomic rearrangements should be included in genetic screening in this population.
基金Supported by The United States Public Health Service(DK067287 and CA162147)the A.Alfred Taubman Medical Research Institute of the University of Michigan
文摘Hereditary non-polyposis colorectal cancer(HNPCC) was previously synonymous with Lynch syndrome; however,identification of the role of germline mutations in the DNA mismatch repair(MMR) genes has made it possible to differentiate Lynch syndrome from other conditions associated with familial colorectal cancer(CRC). Broadly,HNPCC may be dichotomized into conditions that demonstrate defective DNA MMR and microsatellite instability(MSI) vs those conditions that demonstrate intact DNA MMR. Conditions characterized by MMR deficient CRCs include Lynch syndrome(germline MMR mutation),Lynch-like syndrome(biallelic somatic MMR mutations),constitutional MMR deficiency syndrome(biallelic germline MMR mutations),and sporadic MSI CRC(somatic biallelic methylation of MLH1). HNPCC conditions with intact DNA MMR associated with familial CRC include polymerase proofreading associated polyposis and familial colorectal cancer type X. Although next generation sequencing technologies have elucidated the genetic cause for some HNPCC conditions,others remain genetically undefined. Differentiating between Lynch syndrome and the other HNPCC disorders has profound implications for cancer risk assessment and surveillance of affected patients and their at-risk relatives. Clinical suspicion coupled with molecular tumor analysis and testing for germline mutations can help differentiate the clinical mimicry within HNPCC and facilitate diagnosis and management.
基金Supported in part by Tianjin Science Grant,China
文摘AIM： To analyze the frequency of hereditary non-polyposis colorectal cancer （HNPCC） in Chinese colorectal cancer （CRC） patients, and to discuss the value of microsatellite instability （MSI） and/or immunohistochemistry （IHC） for MSH2/MLH1 protein analysis as pre-screening tests in China. METHODS： The Amsterdam criteria Ⅰ and Ⅱ （clinical diagnosis） and/or germline hMLHI/hMSH2 mutations （genetic diagnosis） were used to classify HNPCC families. Genetic tests, including microsatellite instability, immunohistochemistry for MSH2/MLH1 proteins and hMSH2/hMLH1 genes, were performed in each proband. RESULTS： From July 2000 to June 2004, 1988 patients with colorectal cancer were analysed and 114 CRC patients （5.7%） from 48 families were categorized as having HNPCC, including 76 from 26 families diagnosed clinically and 38 from the other 22 families diagnosed genetically. The sensitivity and specificity of high MSI and IHC for predicting mutations were 100% and 54%, and 79% and 77%, respectively. CONCLUSION： The frequency of HNPCC is approximately 10% among all Chinese CRC cases. The MSI and IHC detections for hMSH2/hMLH1 proteins are reliable prescreening tests for hMLHI/hMSH2 germline mutations in families suspected of having HNPCC.
基金Supported by The Initiation Fund for Prominent Young Researchers of Shanghai Medical College,Fudan University
文摘AIM:To study the germline mutation of hPMS2 gene in 26 unrelated Chinese hereditary nonpolyposis colorectal cancer(HNPCC)probands and to fulfill the screening strategy for HNPCC in Chinese.METHODS:Genomic DNA was extracted from the peripheral blood.To avoid the interference of pseudogene in detection of the remaining 11 exons(exon 1-5,9,11-15),long-range polymerase chain reaction(PCR)was conducted to amplify the complete coding region of hPMS2 gene firstly.Then 1/8 of the PCR productswere used as template to amplify the individual exon respectively and DNA sequencing was done.Direct DNA sequencing of the conventional PCR products of exon 6,7,8 and 10 of hPMS2 gene was performed.The same analysis was made in 130 healthy persons without family histories of HNPCC to further investigate the pathological effects of the detected missense mutation.RESULTS:One HNPCC proband fulf illed Bethesda guidelines and was found to carry the germline mutation of hPMS2 gene,which has not been reported in Chinese HNPCC families.It was a missense mutation at c.1532C>T of exon 11.It was detected in three controls as well with an occurrence rate of 2.3%(3/130).Since it could not be found in the PMS2-single nucleotide polymorphism(SNP)database,this missense mutation is a new SNP unreported up to date.Meanwhile,260 reported SNPs of hPMS2 gene were detected in the 26 HNPCC probands.The 2nd and 5th exons were probably the hot SNP regions of hPMS2 gene in Chinese HNPCC families involving 53.1%of all reported SNP.CONCLUSION:The germline mutation of hPMS2 gene may be rare in Chinese HNPCC families.The 2nd and 5th exons are hot SNP regions of hPMS2 gene.
