BACKGROUND Heterozygous familial hypobetalipoproteinemia(FHBL)is a semi-autosomal disorder that is caused mainly by an APOB variant.It is usually asymptomatic and rarely leads to non-alcoholic steatohepatitis(NASH).CA...BACKGROUND Heterozygous familial hypobetalipoproteinemia(FHBL)is a semi-autosomal disorder that is caused mainly by an APOB variant.It is usually asymptomatic and rarely leads to non-alcoholic steatohepatitis(NASH).CASE SUMMARY A 12-year-old boy was referred to our hospital after prolonged elevation of liver enzymes was observed during health checkups in Kagawa Prefecture.Abdominal ultrasound showed a bright liver,and laboratory investigations revealed low lowdensity lipoprotein cholesterol and apolipoprotein B protein levels.His family history included fatty liver and hypolipidemia in his father,which led to a clinical diagnosis of FHBL.A liver biopsy was performed on suspicion of liver fibrosis based on biomarkers.The liver tissue showed fatty steatosis,inflammation,hepatocyte ballooning,and fibrosis,indicating NASH.Genetic testing detected the APOB variant,and the patient was treated successfully with vitamin E.CONCLUSION It is important to assess family history and liver dysfunction severity in non-obese patients with hypolipidemia and fatty liver.展开更多
BACKGROUND Familial Mediterranean fever(FMF)is an autosomal recessive autoinflammatory disorder marked by recurrent episodes of fever and serositis.Resistin,a proinflammatory cytokine,may play a role in FMF pathogenes...BACKGROUND Familial Mediterranean fever(FMF)is an autosomal recessive autoinflammatory disorder marked by recurrent episodes of fever and serositis.Resistin,a proinflammatory cytokine,may play a role in FMF pathogenesis by promoting the release of interleukin-1beta,tumour necrosis factor alpha,and interleukin-6.AIM To evaluate serum resistin levels in children with FMF during acute attacks and remission,and to assess its potential as a biomarker for disease activity and progression.METHODS A case-control study was conducted involving 40 pediatric patients with FMF and 40 age-and sex-matched healthy controls.Serum resistin and inflammatory markers—including total leukocyte count(TLC),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),serum amyloid A(SAA),and fibrinogen—were measured using enzyme-linked immunosorbent assay and standard assays.RESULTS No significant differences were found in age or sex between FMF patients and controls.Among FMF patients,fever was the most prevalent symptom(95%),followed by abdominal pain(75%).The most frequently detected genetic mutation was M694I,followed by M694V,E148Q,M680I,and V726A.Compound heterozygous mutations,including M694I/V726A and M694I/M694V,were equally represented.During acute attacks,FMF patients exhibited significantly elevated levels of TLC,ESR,CRP,SAA,and fibrinogen compared to attack-free periods and controls.Serum resistin levels were markedly higher during acute attacks and showed a strong positive correlation with other acute inflammatory markers.Receiver operating characteristic curve analysis demonstrated high sensitivity and specificity of resistin as a potential biomarker for FMF.CONCLUSION Resistin is significantly elevated in children with FMF during acute episodes and correlates with established inflammatory markers.These findings support its potential role as a non-invasive biomarker for disease activity and severity in pediatric FMF.展开更多
BACKGROUND Familial adenomatous polyposis(FAP)is an autosomal dominant syndrome that results from a germline mutation in the adenomatous polyposis coli gene.It is characterized by the early development of hundreds of ...BACKGROUND Familial adenomatous polyposis(FAP)is an autosomal dominant syndrome that results from a germline mutation in the adenomatous polyposis coli gene.It is characterized by the early development of hundreds of adenomas in the colon during the second decade of life.If prophylactic colectomy is not performed,most patients eventually develop colorectal cancer(CRC).CASE SUMMARY We present the mutational profile of a case of FAP that progressed to CRC.A 45-year-old Saudi man presented with intestinal obstruction and underwent a total colectomy.The colon showed hundreds of polyps and two infiltrative ulcerative lesions,which proved to be adenocarcinoma according to histopathology.We performed next-generation sequencing and found mutations in the TP53,NRAS,EGFR PDGFR,MET,KIT,ERBB2,and GUSP genes.CONCLUSION To the best of our knowledge,this case report is the first to sheds the light on the mutation profile of FAP that progressed to CRC in Saudi Arabia.展开更多
BACKGROUND Progressive familial intrahepatic cholestasis type 1(PFIC-1)is a genetic cholestatic disease causing end-stage liver disease,which needs liver transplantation(LT).Simultaneous biliary diversion(BD)was recom...BACKGROUND Progressive familial intrahepatic cholestasis type 1(PFIC-1)is a genetic cholestatic disease causing end-stage liver disease,which needs liver transplantation(LT).Simultaneous biliary diversion(BD)was recommended to prevent allograft steatosis after transplantation,while increasing the risk of infection.Here,an attempt was made to perform BD using appendix to prevent bacterial translocation after LT.CASE SUMMARY An 11-month-old boy diagnosed with PFIC-1 received ABO compatible living donor LT due to refractory jaundice and pruritus.His mother donated her left lateral segment with a graft-to-recipient weight ratio of 2.9%.Internal BD was constructed during LT using the appendix by connecting its proximal end with the intrahepatic biliary duct and the distal end with colon.Biliary leakage was suspected on the 5th day after transplantation and exploratory laparotomy indicated biliary leakage at the cutting surface of liver.The liver function returned to normal on the 9th day post-operation and maintained normal during the 15-month follow-up.Cholangiography at 10 months after transplantation confirmed the direct secretion of bile into colon.Computerized tomography scan(4 months and 10 months)and liver biopsy(10 months)indicated no steatosis in the allograft.No complaint of recurrent diarrhea,infection or growth retardation was reported during follow-up.CONCLUSION Internal BD using appendix during LT is effective in preventing allograft steatosis and post-transplant infection in PFIC-1 recipients.展开更多
This article reviews a paper in the World Journal of Diabetes.The study uncovers the link between PPARG gene mutations and metabolic disorders,such as insulin resistance,diabetes,and hypertriglyceridemia,and emphasize...This article reviews a paper in the World Journal of Diabetes.The study uncovers the link between PPARG gene mutations and metabolic disorders,such as insulin resistance,diabetes,and hypertriglyceridemia,and emphasizes the crucial role of genetic testing in precise diagnosis and personalized treatment.This article further points out that in-depth investigation into the clinical heterogeneity of PPARG mutations and their underlying mechanisms can contribute to optimizing management strategies.Meanwhile,the development of more effective targeted therapies and the conduct of extensive genomic research are of great significance for understanding familial partial lipodystrophy type 3 and related metabolic syndromes.展开更多
Progressive familial intrahepatic cholestasis(PFIC)is a group of rare,inherited cholestatic liver disorders presenting in infants and children and are associated with impaired bile flow(i.e.,cholestasis),pruritus and ...Progressive familial intrahepatic cholestasis(PFIC)is a group of rare,inherited cholestatic liver disorders presenting in infants and children and are associated with impaired bile flow(i.e.,cholestasis),pruritus and progressive liver disease.Historically there has been no effective or approved pharmacologic treatments for these disorders and standard medical treatment has only been supportive.The impaired bile flow within the liver,leads to accumulation in the liver and inflammation.Historically there has been no effective or approved pharmacologic treatments for these disorders and standard medical treatment has only been supportive.A potential for reducing pathologic bile accumulation in the liver is surgical biliary diversion,with an aim to interrupt the enterohepatic circulation.These procedures have demonstrated a positive effect in PFIC by normalizing serum bile acids,reducing pruritus and liver injury and improving the patient quality of life.Nonsurgical approach to interrupting the enterohepatic circulation is inhibition of the ileal bile acid transporter(IBAT).IBAT inhibition has demonstrated efficacy in reducing serum bile acids and pruritus.We aim to present the 13 types of PFIC and the current evidence on the use of IBAT inhibitors in treating children with PFIC.展开更多
This editorial discusses Wang et al's article on familial gastrointestinal stromal tumors(GISTs).We read with great interest this article concerning the diagnosis,treatment,and post-treatment management of patient...This editorial discusses Wang et al's article on familial gastrointestinal stromal tumors(GISTs).We read with great interest this article concerning the diagnosis,treatment,and post-treatment management of patients with familial GISTs.The actual incidence of GISTs may be underestimated due to diagnostic limitations and the long-term low-risk behavior of some GISTs.The molecular landscape of GISTs is primarily driven by mutations in the KIT and platelet-derived growth factor receptor alpha(PDGFRA)genes.A subset of GISTs without these mutations known as wild-type GISTs,may harbor other rare mutations,impacting their response to targeted therapies.Clinically,patients with GISTs present with nonspecific symptoms,often leading to delayed diagnosis.Genetic predispositions in familial GISTs provide insights into the genetic architecture and extragastrointestinal manifestations of GISTs.Management has evolved from surgical interventions to molecular-based therapies using tyrosine kinase inhibitors.The management of GISTs,especially in familial cases,requires a multidisciplinary approach.Cases of different gene mutations were reported in the same family,suggesting that incorporating genetic testing into routine clinical practice is crucial for the early identification of high-risk individuals and the implementation of tailored surveillance programs.展开更多
AIM:To find out the association of secreted protein acidic and rich in cysteine(SPARC)-related modular calcium binding 2(SMOC2)gene variants rs2255680 and rs13208776 with genotypic and phenotypic characteristics in bo...AIM:To find out the association of secreted protein acidic and rich in cysteine(SPARC)-related modular calcium binding 2(SMOC2)gene variants rs2255680 and rs13208776 with genotypic and phenotypic characteristics in both familial and non-familial primary open angle glaucoma(POAG)patients.METHODS:A total of 212 POAG patients,comprising 124 familial and 88 non-familial,were enrolled.For genotyping the SMOC2 variant rs2255680,amplification refractory mutation system(ARMS)-polymerase chain reaction(PCR)method and PCR-restriction fragment length polymorphism(PCR-RFLP)were utilized for analyzing rs13208776 variant.RESULTS:The mean age of familial POAG patients was 50.92±9.12y,with 78 males and 46 females.The mean age of non-familial POAG patients was 53.14±13.44y,with 52 males and 36 females.The SMOC2 gene variant rs13208776 showed the significant association with POAG between familial and non-familial groups.The homozygous G/G variant was frequent among non-familial(60.2%)whereas the heterozygous G/A variant was more frequent in familial POAG patients(46%).There were significant differences in G/A variant between familial and non-familial glaucoma patients,and the risk was decreased to 0.53-fold in non-familial glaucoma patients[odds ratio(OR):0.53;95%confidence interval(CI):0.29-0.94;P=0.033]in codominant model.The risk was further reduced to 0.49-fold(95%CI:0.28-0.86;P=0.012)in dominant model for non-familial patients.No significant association of SMOC2 gene variant rs2255680 between familial and non-familial glaucoma patients was found in our population.The haplotype analysis showed the decreased risk for TA[OR:0.48(95%CI:0.29-0.79);P=0.004]and an increased risk for TG[OR=2.28(95%CI:1.22-4.25);P=0.01]haplotypes.CONCLUSION:Current findings show significant association of SMOC2 gene variant rs13208776 with POAG between familial and non-familial Pakistani patients.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal(GI)tract,and cases of GISTs tend to be of the disseminated type,with a global incidence of 10 to 15 cases...BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal(GI)tract,and cases of GISTs tend to be of the disseminated type,with a global incidence of 10 to 15 cases/million each year.The rarer familial GISTs,which often represent a population,differ in screening,diagnosis,and treatment.Familial GISTs include primary familial GISTs with predominantly KIT/PDGFRA mutations and wild-type GISTs.However,whether the same genetic family has different phenotypes has not been reported.CASE SUMMARY We report two cases of rare GISTs in the same family:A male patient with the V561D mutation in exon 12 of the PDGFRA gene,who has been taking the targeted drug imatinib since undergoing surgery,and a female patient diagnosed with wild-type GIST,who has been taking imatinib for 3 years since undergoing surgery.The favorable prognosis of these patients during the 7-year follow-up period validates the accuracy of our treatment strategy,and we have refined the entire process of diagnosis and treatment of familial GISTs in order to better manage this rare familial disease.CONCLUSION Different mutation types of familial GISTs in the same family are very rare,thus it is very important to make the correct diagnosis and treatment strategies according to the results of molecular detection for the management of familial GISTs.展开更多
BACKGROUND Familial partial lipodystrophy disease(FPLD)is a collection of rare genetic diseases featuring partial loss of adipose tissue.However,metabolic difficulties,such as severe insulin resistance,diabetes,hypert...BACKGROUND Familial partial lipodystrophy disease(FPLD)is a collection of rare genetic diseases featuring partial loss of adipose tissue.However,metabolic difficulties,such as severe insulin resistance,diabetes,hypertriglyceridemia,and hyperte-nsion frequently occur alongside adipose tissue loss,making it susceptible misdiagnosis and delaying effective treatment.Numerous genes are implicated the occurrence of FPLD,and genetic testing has been for conditions linked single gene mutation related to FPLD.Reviewing recent reports,treatment of the disease is limited to preventing and improving complications in patients.In 2017,a 31-year-old woman with diabetes,hypertension and hypertriglyceri-demia was hospitalized.We identified a mutation in her peroxisome proliferator-activated receptor gamma(PPARG)gene,Y151C(p.Tyr151Cys),which results in a nucleotide substitution residue 452 in the DNA-binding domain(DBD)of PPARG.The unaffected family member did not carry this mutation.Pioglitazone,a PPARG agonist,improved the patient’s responsiveness to hypoglycemic and antihyper-tensive therapy.After one year of treatment in our hospital,the fasting blood glucose and glycosylated hemoglobin of the patient were close to normal.展开更多
Amyotrophi c lateral s c lerosis(ALS)and frontotemporal dementia(FTD)are two closely related disorders with overlapping clinical,genetic,and neuropathological features,forming a continuous disease spectrum(Ling et al....Amyotrophi c lateral s c lerosis(ALS)and frontotemporal dementia(FTD)are two closely related disorders with overlapping clinical,genetic,and neuropathological features,forming a continuous disease spectrum(Ling et al.,2013).The major pathological hallmark of ALS and FTD are the depletion from the nucleus of the RNA-binding proteins TAR DNA‐binding protein 43(TDP-43)and FUsed in Sarcoma(FUS)and their abnormal accumulation in ubiquitin-positive cytoplasmic inclusions(Ling et al.,2013).展开更多
BACKGROUND Immature ovarian teratoma is a rare and aggressive neoplasm that affects young women.This report is the first to describe the development of immature teratoma after ovarian cystectomy for mature teratoma of...BACKGROUND Immature ovarian teratoma is a rare and aggressive neoplasm that affects young women.This report is the first to describe the development of immature teratoma after ovarian cystectomy for mature teratoma of the ovary in an adolescent female with a family history of ovarian teratoma.CASE SUMMARY A 16-year-old girl who had undergone bilateral ovarian cystectomy for mature teratomas 3 years ago showed bilateral adnexal tumors during her regular ultrasonography follow-up every 6 months.She received laparoscopic bilateral ovarian cystectomy,and final histopathology showed grade-1 immature teratoma of the left ovary and mature teratoma of the right ovary.Laparoscopic left salpingo-oophorectomy and staging procedures were performed again.Her mother,maternal aunt,and maternal grandmother had also received surgeries for mature ovarian teratomas.CONCLUSION It is important to have guidance on management of patient and family members with familial ovarian teratomas.展开更多
Familial hypercholesterolemia(FH)is characterized by elevated low-density lipoprotein cholesterol levels due to genetic mutations,presenting with xanthomas,corneal arch,and severe cardiovascular diseases.Early identif...Familial hypercholesterolemia(FH)is characterized by elevated low-density lipoprotein cholesterol levels due to genetic mutations,presenting with xanthomas,corneal arch,and severe cardiovascular diseases.Early identification,diagnosis,and treatment are crucial to prevent severe complications like acute myocardial infarction.Statins are the primary treatment,supplemented by Ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors,though their effectiveness can be limited in severe cases.Over 90%of FH cases remain undiagnosed,and current treatments are often inadequate,underscoring the need for improved diagnostic and management systems.Future strategies include advancements in gene testing,precision medicine,and novel drugs,along with gene therapy approaches like AAV-mediated gene therapy and clustered regularly interspaced short palindromic repeats.Lifestyle modifications,including health education,dietary control,and regular exercise,are essential for managing FH and preventing related diseases.Research into FH-related gene mutations,especially LDLR,is critical for accurate diagnosis and effective treatment.展开更多
Introduction: Spondyloarthritis (SpA) comprises a group of chronic inflammatory rheumatic diseases characterized by predominant axial involvement. These include ankylosing spondylitis (AS), reactive arthritis (ReA), p...Introduction: Spondyloarthritis (SpA) comprises a group of chronic inflammatory rheumatic diseases characterized by predominant axial involvement. These include ankylosing spondylitis (AS), reactive arthritis (ReA), psoriatic arthritis (PsA), arthritis associated with inflammatory bowel diseases (IBD), SAPHO syndrome (Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis), juvenile spondyloarthritis (JSPA), and undifferentiated SpA. Their exact cause is unknown but is believed to stem from a combination of factors. The first familial forms were described by de Blécourt et al. in 1961. The objective was to evaluate the epidemiological, clinical, therapeutic and evolutionary aspects of familial forms of SpA and in particular, to prove the severity of the disease in family members compared to index cases in the rheumatology department of the Aristide Le Dantec University Hospital in Dakar. Methodology: This was a prospective, cross-sectional and descriptive study with an analytical aim on patients with the familial form of spondyloarthritis defined by the existence of at least one other family member with SpA outside the propositus, collected within the Aristide Le Dantec rheumatology department in Dakar over a period of 10 years between January 2012 and December 2021. There were two phases of study, the first of which consisted of collecting index cases with miserly SpA and the second of which consisted of family screening after consent. The data analysed were epidemiological, clinical, paraclinical, therapeutic and evolving. Results: Out of 100 families of 1905 members, 667 SpA patients included, i.e. a prevalence of 35%, including 225 (33.73%) men and 412 women (61.17%), i.e. a ratio of 1.8. The mean age at diagnosis among relatives was 26.3 years (range 13 and 80 years), 47.14 years among the propositus, in whom the mean age at onset was 36.26 years and that of relatives 49.9 years in the first degree, 15 years in the second degree and 1 year in the third degree. The time to diagnosis was 11.20 years in the first degree, 2.5 years in the second degree, 1 year in the third degree and 10.88 years in the case of the proposes. The number of marriages in families was 420 of which 116 were consanguineous (consanguinity rate 27.62%), 19% among the propositus. HLA-B27 positive in 92% of the proposers and 33.43% in the families;70% of the propositus had an inflammatory syndrome and 17.54% in the families;87% of sacroilliitis in the propositus and 5.54% in the families. Clinical forms were dominated by undifferentiated SpA (338 cases) and APS (295 cases). The average BASFI was 3.23 on D0;2.59 in the 3rd month and 1 in the 6th month for the propositus versus 2.55 at D0;1.86 at the 3rd month and 1.55 in the 6th month in the families. Average BASDAI was 3.92 at D0;3.12 at the 3rd month and 2.07 at the 6th month in the propositus and 3 at D0;2.21 at the 3rd month and 1 at the 6th month in the families. Autoimmune associated conditions were 18 cases, degenerative 24 cases, autoinflammatory 2 metabolic cases 18 cases. They all received: NSAIDs, methotrexate, salazopyrine (11 cases) and anti-TNF-α (1 case). The evolution was generally favourable. Conclusion: SpA is on the rise in Senegalese hospitals, frequent in young people, SPA and undifferentiated SpA are the most frequent, management is essentially based on conventional care, and the disease is less severe in family members than index cases.展开更多
BACKGROUND Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy(SG)between patients with familial aggregation of obesity(FAO)and patients with sporadic obesity(SO)have not ...BACKGROUND Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy(SG)between patients with familial aggregation of obesity(FAO)and patients with sporadic obesity(SO)have not been elucidated.AIM To explore the impact of SG on weight loss and the alleviation of obesity-related comorbidities in individuals with FAO.METHODS A total of 193 patients with obesity who underwent SG were selected.Patients with FAO/SO were matched 1:1 by propensity score matching and were categorized into 4 groups based on the number of first-degree relatives with obesity(1 SO vs 1FAO,2SO vs 2FAO).The baseline characteristics,weight loss outcomes,prevalence of obesity-related comorbidities and incidence of major surgeryrelated complications were compared between groups.RESULTS We defined FAO as the presence of two or more first-degree relatives with obesity.Patients with FAO did not initially show significant differences in baseline data,short-term postoperative weight loss,or obesity-related comorbidities when compared to patients with SO preoperatively.However,distinctions between the two groups became evident at the two-year mark,with statistically significant differences in both percentage of total weight loss(P=0.006)and percentage of excess weight loss(P<0.001).The FAO group exhibited weaker remission of type 2 diabetes mellitus(T2DM)(P=0.031),hyperlipidemia(P=0.012),and non-alcoholic fatty liver disease(NAFLD)(P=0.003)as well as a lower incidence of acid reflux(P=0.038).CONCLUSION FAO patients is associated with decreased mid-to-long-term weight loss outcomes;the alleviation of T2DM,hyperlipidemia and NAFLD;and decreased incidence of acid reflux postoperatively.展开更多
Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretio...Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretion,and/or caused by defects in the secretory machinery of cholangiocytes.Several mutations and pathways that lead to cholestasis have been described.Progressive familial intrahepatic cholestasis(PFIC)is a group of rare diseases caused by autosomal recessive mutations in the genes that encode proteins expressed mainly in the apical membrane of the hepatocytes.PFIC 1,also known as Byler’s disease,is caused by mutations of the ATP8B1 gene,which encodes the familial intrahepatic cholestasis 1 protein.PFIC 2 is characterized by the downregulation or absence of functional bile salt export pump(BSEP)expression via variations in the ABCB11 gene.Mutations of the ABCB4 gene result in lower expression of the multidrug resistance class 3 glycoprotein,leading to the third type of PFIC.Newer variations of this disease have been described.Loss of function of the tight junction protein 2 protein results in PFIC 4,while mutations of the NR1H4 gene,which encodes farnesoid X receptor,an important transcription factor for bile formation,cause PFIC 5.A recently described type of PFIC is associated with a mutation in the MYO5B gene,important for the trafficking of BSEP and hepatocyte membrane polarization.In this review,we provide a brief overview of the molecular mechanisms and clinical features associated with each type of PFIC based on peer reviewed journals published between 1993 and 2020.展开更多
Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system whi...Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD pathogenesis, defining the specific contribution to familial IBD of each one of these factors might have also clinical usefulness. We review the available evidence on familial IBD pathogenesis.展开更多
In order to compare the clinical characteristics of familial and non-familial bullous lichen planus (BLP), the archival data of 36 BLP patients with positive family history and 21 BLP patients with negative family his...In order to compare the clinical characteristics of familial and non-familial bullous lichen planus (BLP), the archival data of 36 BLP patients with positive family history and 21 BLP patients with negative family history diagnosed according to the clinical features and histopathology were collected in our department from 1956 to 2003. The clinical features were analyzed and compared. There were significant differences between familial and non-familial BLP in age of onset, duration of disease and extension of eruption (P<0.01). It was concluded that familial BLP appeared to differ from the non-familial form in its earlier age of onset, longer duration of the disease, more extensive eruption and more tendency to involve nails. Hereditary factors may play a role in the pathogenesis of familial BLP.展开更多
Genotyping is conclusive for the diagnosis of progressive familial intrahepatic cholestasis type 3(PFIC3). Here we report a Chinese patient of PFIC3 with compound mutations in the ABCB4 gene. Liver biopsy was performe...Genotyping is conclusive for the diagnosis of progressive familial intrahepatic cholestasis type 3(PFIC3). Here we report a Chinese patient of PFIC3 with compound mutations in the ABCB4 gene. Liver biopsy was performed on a 17-year-old male patient with intrahepatic cholestasis of unknown etiology. Liver histology findings are indicative of intrahepatic cholestasis with extensive fibrosis. Genotyping revealed c.175C>T(p.L59L) mutation in exon 4, c.504C>T(p.N168N) mutation in exon 6, c.711A>T(p.I237I) mutation in exon 8, c.874A>T(p.K292X) in exon 9 and a novel mutation, c.1804G>T(p.G602W) in exon 15. Based on these findings, the patient was diagnosed with PFIC3. The novel mutation p.G602 W in exon 15 was predicted as probably damaging by Poly Phen-2 with a score of 0.986(sensitivity: 0.54; specificity: 0.94) and was predicted to affect protein function with a SIFT score of 0.01.展开更多
BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resul...BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resulting in a hepatocellular form of cholestasis.While the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause,recent scientific advancements have uncovered multiple specific responsible proteins.The variety of identified defects has resulted in an ever-broadening phenotypic spectrum,ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver disease.AIM To review current data on defects in bile acid homeostasis,explore the expanding knowledge base of genetic based diseases in this field,and report disease characteristics and management.METHODS We conducted a systemic review according to PRISMA guidelines.We performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding,diagnosis,and management of bile acid homeostasis with a focus on the family of diseases collectively known as PFIC.English only articles were accessed in full.The manual search included references of retrieved articles.We extracted data on disease characteristics,associations with other diseases,and treatment.Data was summarized and presented in text,figure,and table format.RESULTS Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults.A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common phenotype.CONCLUSION We present a summary of current advances made in a number of areas relevant to both the classically described FIC1(ATP8B1),BSEP(ABCB11),and MDR3(ABCB4)transporter deficiencies,as well as more recently described gene mutations--TJP2(TJP2),FXR(NR1H4),MYO5B(MYO5B),and others which expand the etiology and understanding of PFIC-related cholestatic diseases and bile transport.展开更多
文摘BACKGROUND Heterozygous familial hypobetalipoproteinemia(FHBL)is a semi-autosomal disorder that is caused mainly by an APOB variant.It is usually asymptomatic and rarely leads to non-alcoholic steatohepatitis(NASH).CASE SUMMARY A 12-year-old boy was referred to our hospital after prolonged elevation of liver enzymes was observed during health checkups in Kagawa Prefecture.Abdominal ultrasound showed a bright liver,and laboratory investigations revealed low lowdensity lipoprotein cholesterol and apolipoprotein B protein levels.His family history included fatty liver and hypolipidemia in his father,which led to a clinical diagnosis of FHBL.A liver biopsy was performed on suspicion of liver fibrosis based on biomarkers.The liver tissue showed fatty steatosis,inflammation,hepatocyte ballooning,and fibrosis,indicating NASH.Genetic testing detected the APOB variant,and the patient was treated successfully with vitamin E.CONCLUSION It is important to assess family history and liver dysfunction severity in non-obese patients with hypolipidemia and fatty liver.
文摘BACKGROUND Familial Mediterranean fever(FMF)is an autosomal recessive autoinflammatory disorder marked by recurrent episodes of fever and serositis.Resistin,a proinflammatory cytokine,may play a role in FMF pathogenesis by promoting the release of interleukin-1beta,tumour necrosis factor alpha,and interleukin-6.AIM To evaluate serum resistin levels in children with FMF during acute attacks and remission,and to assess its potential as a biomarker for disease activity and progression.METHODS A case-control study was conducted involving 40 pediatric patients with FMF and 40 age-and sex-matched healthy controls.Serum resistin and inflammatory markers—including total leukocyte count(TLC),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),serum amyloid A(SAA),and fibrinogen—were measured using enzyme-linked immunosorbent assay and standard assays.RESULTS No significant differences were found in age or sex between FMF patients and controls.Among FMF patients,fever was the most prevalent symptom(95%),followed by abdominal pain(75%).The most frequently detected genetic mutation was M694I,followed by M694V,E148Q,M680I,and V726A.Compound heterozygous mutations,including M694I/V726A and M694I/M694V,were equally represented.During acute attacks,FMF patients exhibited significantly elevated levels of TLC,ESR,CRP,SAA,and fibrinogen compared to attack-free periods and controls.Serum resistin levels were markedly higher during acute attacks and showed a strong positive correlation with other acute inflammatory markers.Receiver operating characteristic curve analysis demonstrated high sensitivity and specificity of resistin as a potential biomarker for FMF.CONCLUSION Resistin is significantly elevated in children with FMF during acute episodes and correlates with established inflammatory markers.These findings support its potential role as a non-invasive biomarker for disease activity and severity in pediatric FMF.
文摘BACKGROUND Familial adenomatous polyposis(FAP)is an autosomal dominant syndrome that results from a germline mutation in the adenomatous polyposis coli gene.It is characterized by the early development of hundreds of adenomas in the colon during the second decade of life.If prophylactic colectomy is not performed,most patients eventually develop colorectal cancer(CRC).CASE SUMMARY We present the mutational profile of a case of FAP that progressed to CRC.A 45-year-old Saudi man presented with intestinal obstruction and underwent a total colectomy.The colon showed hundreds of polyps and two infiltrative ulcerative lesions,which proved to be adenocarcinoma according to histopathology.We performed next-generation sequencing and found mutations in the TP53,NRAS,EGFR PDGFR,MET,KIT,ERBB2,and GUSP genes.CONCLUSION To the best of our knowledge,this case report is the first to sheds the light on the mutation profile of FAP that progressed to CRC in Saudi Arabia.
基金Supported by the National Natural Science Foundation of China,No.82471804.
文摘BACKGROUND Progressive familial intrahepatic cholestasis type 1(PFIC-1)is a genetic cholestatic disease causing end-stage liver disease,which needs liver transplantation(LT).Simultaneous biliary diversion(BD)was recommended to prevent allograft steatosis after transplantation,while increasing the risk of infection.Here,an attempt was made to perform BD using appendix to prevent bacterial translocation after LT.CASE SUMMARY An 11-month-old boy diagnosed with PFIC-1 received ABO compatible living donor LT due to refractory jaundice and pruritus.His mother donated her left lateral segment with a graft-to-recipient weight ratio of 2.9%.Internal BD was constructed during LT using the appendix by connecting its proximal end with the intrahepatic biliary duct and the distal end with colon.Biliary leakage was suspected on the 5th day after transplantation and exploratory laparotomy indicated biliary leakage at the cutting surface of liver.The liver function returned to normal on the 9th day post-operation and maintained normal during the 15-month follow-up.Cholangiography at 10 months after transplantation confirmed the direct secretion of bile into colon.Computerized tomography scan(4 months and 10 months)and liver biopsy(10 months)indicated no steatosis in the allograft.No complaint of recurrent diarrhea,infection or growth retardation was reported during follow-up.CONCLUSION Internal BD using appendix during LT is effective in preventing allograft steatosis and post-transplant infection in PFIC-1 recipients.
文摘This article reviews a paper in the World Journal of Diabetes.The study uncovers the link between PPARG gene mutations and metabolic disorders,such as insulin resistance,diabetes,and hypertriglyceridemia,and emphasizes the crucial role of genetic testing in precise diagnosis and personalized treatment.This article further points out that in-depth investigation into the clinical heterogeneity of PPARG mutations and their underlying mechanisms can contribute to optimizing management strategies.Meanwhile,the development of more effective targeted therapies and the conduct of extensive genomic research are of great significance for understanding familial partial lipodystrophy type 3 and related metabolic syndromes.
文摘Progressive familial intrahepatic cholestasis(PFIC)is a group of rare,inherited cholestatic liver disorders presenting in infants and children and are associated with impaired bile flow(i.e.,cholestasis),pruritus and progressive liver disease.Historically there has been no effective or approved pharmacologic treatments for these disorders and standard medical treatment has only been supportive.The impaired bile flow within the liver,leads to accumulation in the liver and inflammation.Historically there has been no effective or approved pharmacologic treatments for these disorders and standard medical treatment has only been supportive.A potential for reducing pathologic bile accumulation in the liver is surgical biliary diversion,with an aim to interrupt the enterohepatic circulation.These procedures have demonstrated a positive effect in PFIC by normalizing serum bile acids,reducing pruritus and liver injury and improving the patient quality of life.Nonsurgical approach to interrupting the enterohepatic circulation is inhibition of the ileal bile acid transporter(IBAT).IBAT inhibition has demonstrated efficacy in reducing serum bile acids and pruritus.We aim to present the 13 types of PFIC and the current evidence on the use of IBAT inhibitors in treating children with PFIC.
基金National Natural Science Foundation of China,No.82370569Basic and Applied Basic Research Foundation of Guangdong Province,No.2022A1515012647the Key Program for Science and Technology Projects of Social Development in Zhuhai,No.2220004000249(to Li XF).
文摘This editorial discusses Wang et al's article on familial gastrointestinal stromal tumors(GISTs).We read with great interest this article concerning the diagnosis,treatment,and post-treatment management of patients with familial GISTs.The actual incidence of GISTs may be underestimated due to diagnostic limitations and the long-term low-risk behavior of some GISTs.The molecular landscape of GISTs is primarily driven by mutations in the KIT and platelet-derived growth factor receptor alpha(PDGFRA)genes.A subset of GISTs without these mutations known as wild-type GISTs,may harbor other rare mutations,impacting their response to targeted therapies.Clinically,patients with GISTs present with nonspecific symptoms,often leading to delayed diagnosis.Genetic predispositions in familial GISTs provide insights into the genetic architecture and extragastrointestinal manifestations of GISTs.Management has evolved from surgical interventions to molecular-based therapies using tyrosine kinase inhibitors.The management of GISTs,especially in familial cases,requires a multidisciplinary approach.Cases of different gene mutations were reported in the same family,suggesting that incorporating genetic testing into routine clinical practice is crucial for the early identification of high-risk individuals and the implementation of tailored surveillance programs.
基金Supported by Higher Education Commission of Pakistan(NRPU#2835)Pakistan Science Foundation Project No.Biotech 101,funded to Professor Dr.Ali Muhammad Waryah.
文摘AIM:To find out the association of secreted protein acidic and rich in cysteine(SPARC)-related modular calcium binding 2(SMOC2)gene variants rs2255680 and rs13208776 with genotypic and phenotypic characteristics in both familial and non-familial primary open angle glaucoma(POAG)patients.METHODS:A total of 212 POAG patients,comprising 124 familial and 88 non-familial,were enrolled.For genotyping the SMOC2 variant rs2255680,amplification refractory mutation system(ARMS)-polymerase chain reaction(PCR)method and PCR-restriction fragment length polymorphism(PCR-RFLP)were utilized for analyzing rs13208776 variant.RESULTS:The mean age of familial POAG patients was 50.92±9.12y,with 78 males and 46 females.The mean age of non-familial POAG patients was 53.14±13.44y,with 52 males and 36 females.The SMOC2 gene variant rs13208776 showed the significant association with POAG between familial and non-familial groups.The homozygous G/G variant was frequent among non-familial(60.2%)whereas the heterozygous G/A variant was more frequent in familial POAG patients(46%).There were significant differences in G/A variant between familial and non-familial glaucoma patients,and the risk was decreased to 0.53-fold in non-familial glaucoma patients[odds ratio(OR):0.53;95%confidence interval(CI):0.29-0.94;P=0.033]in codominant model.The risk was further reduced to 0.49-fold(95%CI:0.28-0.86;P=0.012)in dominant model for non-familial patients.No significant association of SMOC2 gene variant rs2255680 between familial and non-familial glaucoma patients was found in our population.The haplotype analysis showed the decreased risk for TA[OR:0.48(95%CI:0.29-0.79);P=0.004]and an increased risk for TG[OR=2.28(95%CI:1.22-4.25);P=0.01]haplotypes.CONCLUSION:Current findings show significant association of SMOC2 gene variant rs13208776 with POAG between familial and non-familial Pakistani patients.
基金National Natural Science Foundation of China,No.82160842Clinical Research Project of Research Fund of Gansu Provincial Hospital,No.23GSSYD-17General Program of the Joint Scientific Research Fund,No.23JRRA1521.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are the most common mesenchymal tumors of the gastrointestinal(GI)tract,and cases of GISTs tend to be of the disseminated type,with a global incidence of 10 to 15 cases/million each year.The rarer familial GISTs,which often represent a population,differ in screening,diagnosis,and treatment.Familial GISTs include primary familial GISTs with predominantly KIT/PDGFRA mutations and wild-type GISTs.However,whether the same genetic family has different phenotypes has not been reported.CASE SUMMARY We report two cases of rare GISTs in the same family:A male patient with the V561D mutation in exon 12 of the PDGFRA gene,who has been taking the targeted drug imatinib since undergoing surgery,and a female patient diagnosed with wild-type GIST,who has been taking imatinib for 3 years since undergoing surgery.The favorable prognosis of these patients during the 7-year follow-up period validates the accuracy of our treatment strategy,and we have refined the entire process of diagnosis and treatment of familial GISTs in order to better manage this rare familial disease.CONCLUSION Different mutation types of familial GISTs in the same family are very rare,thus it is very important to make the correct diagnosis and treatment strategies according to the results of molecular detection for the management of familial GISTs.
文摘BACKGROUND Familial partial lipodystrophy disease(FPLD)is a collection of rare genetic diseases featuring partial loss of adipose tissue.However,metabolic difficulties,such as severe insulin resistance,diabetes,hypertriglyceridemia,and hyperte-nsion frequently occur alongside adipose tissue loss,making it susceptible misdiagnosis and delaying effective treatment.Numerous genes are implicated the occurrence of FPLD,and genetic testing has been for conditions linked single gene mutation related to FPLD.Reviewing recent reports,treatment of the disease is limited to preventing and improving complications in patients.In 2017,a 31-year-old woman with diabetes,hypertension and hypertriglyceri-demia was hospitalized.We identified a mutation in her peroxisome proliferator-activated receptor gamma(PPARG)gene,Y151C(p.Tyr151Cys),which results in a nucleotide substitution residue 452 in the DNA-binding domain(DBD)of PPARG.The unaffected family member did not carry this mutation.Pioglitazone,a PPARG agonist,improved the patient’s responsiveness to hypoglycemic and antihyper-tensive therapy.After one year of treatment in our hospital,the fasting blood glucose and glycosylated hemoglobin of the patient were close to normal.
基金supported by AriSLA Foundation(MLOpathy and SUMOsolvable)Banca d’Italia+2 种基金German Research Foundation(DFGWE 1406/16-1)ALS Stichting grant“The Dutch ALS Tissue Bank”(to SC)。
文摘Amyotrophi c lateral s c lerosis(ALS)and frontotemporal dementia(FTD)are two closely related disorders with overlapping clinical,genetic,and neuropathological features,forming a continuous disease spectrum(Ling et al.,2013).The major pathological hallmark of ALS and FTD are the depletion from the nucleus of the RNA-binding proteins TAR DNA‐binding protein 43(TDP-43)and FUsed in Sarcoma(FUS)and their abnormal accumulation in ubiquitin-positive cytoplasmic inclusions(Ling et al.,2013).
文摘BACKGROUND Immature ovarian teratoma is a rare and aggressive neoplasm that affects young women.This report is the first to describe the development of immature teratoma after ovarian cystectomy for mature teratoma of the ovary in an adolescent female with a family history of ovarian teratoma.CASE SUMMARY A 16-year-old girl who had undergone bilateral ovarian cystectomy for mature teratomas 3 years ago showed bilateral adnexal tumors during her regular ultrasonography follow-up every 6 months.She received laparoscopic bilateral ovarian cystectomy,and final histopathology showed grade-1 immature teratoma of the left ovary and mature teratoma of the right ovary.Laparoscopic left salpingo-oophorectomy and staging procedures were performed again.Her mother,maternal aunt,and maternal grandmother had also received surgeries for mature ovarian teratomas.CONCLUSION It is important to have guidance on management of patient and family members with familial ovarian teratomas.
基金Supported by National Key Research and Development Program of China,No.2022YFE0209900.
文摘Familial hypercholesterolemia(FH)is characterized by elevated low-density lipoprotein cholesterol levels due to genetic mutations,presenting with xanthomas,corneal arch,and severe cardiovascular diseases.Early identification,diagnosis,and treatment are crucial to prevent severe complications like acute myocardial infarction.Statins are the primary treatment,supplemented by Ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors,though their effectiveness can be limited in severe cases.Over 90%of FH cases remain undiagnosed,and current treatments are often inadequate,underscoring the need for improved diagnostic and management systems.Future strategies include advancements in gene testing,precision medicine,and novel drugs,along with gene therapy approaches like AAV-mediated gene therapy and clustered regularly interspaced short palindromic repeats.Lifestyle modifications,including health education,dietary control,and regular exercise,are essential for managing FH and preventing related diseases.Research into FH-related gene mutations,especially LDLR,is critical for accurate diagnosis and effective treatment.
文摘Introduction: Spondyloarthritis (SpA) comprises a group of chronic inflammatory rheumatic diseases characterized by predominant axial involvement. These include ankylosing spondylitis (AS), reactive arthritis (ReA), psoriatic arthritis (PsA), arthritis associated with inflammatory bowel diseases (IBD), SAPHO syndrome (Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis), juvenile spondyloarthritis (JSPA), and undifferentiated SpA. Their exact cause is unknown but is believed to stem from a combination of factors. The first familial forms were described by de Blécourt et al. in 1961. The objective was to evaluate the epidemiological, clinical, therapeutic and evolutionary aspects of familial forms of SpA and in particular, to prove the severity of the disease in family members compared to index cases in the rheumatology department of the Aristide Le Dantec University Hospital in Dakar. Methodology: This was a prospective, cross-sectional and descriptive study with an analytical aim on patients with the familial form of spondyloarthritis defined by the existence of at least one other family member with SpA outside the propositus, collected within the Aristide Le Dantec rheumatology department in Dakar over a period of 10 years between January 2012 and December 2021. There were two phases of study, the first of which consisted of collecting index cases with miserly SpA and the second of which consisted of family screening after consent. The data analysed were epidemiological, clinical, paraclinical, therapeutic and evolving. Results: Out of 100 families of 1905 members, 667 SpA patients included, i.e. a prevalence of 35%, including 225 (33.73%) men and 412 women (61.17%), i.e. a ratio of 1.8. The mean age at diagnosis among relatives was 26.3 years (range 13 and 80 years), 47.14 years among the propositus, in whom the mean age at onset was 36.26 years and that of relatives 49.9 years in the first degree, 15 years in the second degree and 1 year in the third degree. The time to diagnosis was 11.20 years in the first degree, 2.5 years in the second degree, 1 year in the third degree and 10.88 years in the case of the proposes. The number of marriages in families was 420 of which 116 were consanguineous (consanguinity rate 27.62%), 19% among the propositus. HLA-B27 positive in 92% of the proposers and 33.43% in the families;70% of the propositus had an inflammatory syndrome and 17.54% in the families;87% of sacroilliitis in the propositus and 5.54% in the families. Clinical forms were dominated by undifferentiated SpA (338 cases) and APS (295 cases). The average BASFI was 3.23 on D0;2.59 in the 3rd month and 1 in the 6th month for the propositus versus 2.55 at D0;1.86 at the 3rd month and 1.55 in the 6th month in the families. Average BASDAI was 3.92 at D0;3.12 at the 3rd month and 2.07 at the 6th month in the propositus and 3 at D0;2.21 at the 3rd month and 1 at the 6th month in the families. Autoimmune associated conditions were 18 cases, degenerative 24 cases, autoinflammatory 2 metabolic cases 18 cases. They all received: NSAIDs, methotrexate, salazopyrine (11 cases) and anti-TNF-α (1 case). The evolution was generally favourable. Conclusion: SpA is on the rise in Senegalese hospitals, frequent in young people, SPA and undifferentiated SpA are the most frequent, management is essentially based on conventional care, and the disease is less severe in family members than index cases.
文摘BACKGROUND Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy(SG)between patients with familial aggregation of obesity(FAO)and patients with sporadic obesity(SO)have not been elucidated.AIM To explore the impact of SG on weight loss and the alleviation of obesity-related comorbidities in individuals with FAO.METHODS A total of 193 patients with obesity who underwent SG were selected.Patients with FAO/SO were matched 1:1 by propensity score matching and were categorized into 4 groups based on the number of first-degree relatives with obesity(1 SO vs 1FAO,2SO vs 2FAO).The baseline characteristics,weight loss outcomes,prevalence of obesity-related comorbidities and incidence of major surgeryrelated complications were compared between groups.RESULTS We defined FAO as the presence of two or more first-degree relatives with obesity.Patients with FAO did not initially show significant differences in baseline data,short-term postoperative weight loss,or obesity-related comorbidities when compared to patients with SO preoperatively.However,distinctions between the two groups became evident at the two-year mark,with statistically significant differences in both percentage of total weight loss(P=0.006)and percentage of excess weight loss(P<0.001).The FAO group exhibited weaker remission of type 2 diabetes mellitus(T2DM)(P=0.031),hyperlipidemia(P=0.012),and non-alcoholic fatty liver disease(NAFLD)(P=0.003)as well as a lower incidence of acid reflux(P=0.038).CONCLUSION FAO patients is associated with decreased mid-to-long-term weight loss outcomes;the alleviation of T2DM,hyperlipidemia and NAFLD;and decreased incidence of acid reflux postoperatively.
基金Supported by NIH,No.UG3TR003289 to Soto-Gutierrez A.
文摘Cholestasis is a clinical condition resulting from the imapairment of bile flow.This condition could be caused by defects of the hepatocytes,which are responsible for the complex process of bile formation and secretion,and/or caused by defects in the secretory machinery of cholangiocytes.Several mutations and pathways that lead to cholestasis have been described.Progressive familial intrahepatic cholestasis(PFIC)is a group of rare diseases caused by autosomal recessive mutations in the genes that encode proteins expressed mainly in the apical membrane of the hepatocytes.PFIC 1,also known as Byler’s disease,is caused by mutations of the ATP8B1 gene,which encodes the familial intrahepatic cholestasis 1 protein.PFIC 2 is characterized by the downregulation or absence of functional bile salt export pump(BSEP)expression via variations in the ABCB11 gene.Mutations of the ABCB4 gene result in lower expression of the multidrug resistance class 3 glycoprotein,leading to the third type of PFIC.Newer variations of this disease have been described.Loss of function of the tight junction protein 2 protein results in PFIC 4,while mutations of the NR1H4 gene,which encodes farnesoid X receptor,an important transcription factor for bile formation,cause PFIC 5.A recently described type of PFIC is associated with a mutation in the MYO5B gene,important for the trafficking of BSEP and hepatocyte membrane polarization.In this review,we provide a brief overview of the molecular mechanisms and clinical features associated with each type of PFIC based on peer reviewed journals published between 1993 and 2020.
基金Supported by Grants from Ministerio de Ciencia e Innovación(SAF2008/03676) and Fundació Miarnau to Sans M
文摘Inflammatory bowel disease (IBD) develops in genetically susceptible individuals due to the influence of environmental factors, leading to an abnormal recognition of microbiota antigens by the innate immune system which triggers an exaggerated immune response and subsequent bowel tissue damage. IBD has been more frequently found in families, an observation that could be due to either genetic, environmental or both types of factors present in these families. In addition to expanding our knowledge on IBD pathogenesis, defining the specific contribution to familial IBD of each one of these factors might have also clinical usefulness. We review the available evidence on familial IBD pathogenesis.
文摘In order to compare the clinical characteristics of familial and non-familial bullous lichen planus (BLP), the archival data of 36 BLP patients with positive family history and 21 BLP patients with negative family history diagnosed according to the clinical features and histopathology were collected in our department from 1956 to 2003. The clinical features were analyzed and compared. There were significant differences between familial and non-familial BLP in age of onset, duration of disease and extension of eruption (P<0.01). It was concluded that familial BLP appeared to differ from the non-familial form in its earlier age of onset, longer duration of the disease, more extensive eruption and more tendency to involve nails. Hereditary factors may play a role in the pathogenesis of familial BLP.
文摘Genotyping is conclusive for the diagnosis of progressive familial intrahepatic cholestasis type 3(PFIC3). Here we report a Chinese patient of PFIC3 with compound mutations in the ABCB4 gene. Liver biopsy was performed on a 17-year-old male patient with intrahepatic cholestasis of unknown etiology. Liver histology findings are indicative of intrahepatic cholestasis with extensive fibrosis. Genotyping revealed c.175C>T(p.L59L) mutation in exon 4, c.504C>T(p.N168N) mutation in exon 6, c.711A>T(p.I237I) mutation in exon 8, c.874A>T(p.K292X) in exon 9 and a novel mutation, c.1804G>T(p.G602W) in exon 15. Based on these findings, the patient was diagnosed with PFIC3. The novel mutation p.G602 W in exon 15 was predicted as probably damaging by Poly Phen-2 with a score of 0.986(sensitivity: 0.54; specificity: 0.94) and was predicted to affect protein function with a SIFT score of 0.01.
文摘BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)refers to a disparate group of autosomal recessive disorders that are linked by the inability to appropriately form and excrete bile from hepatocytes,resulting in a hepatocellular form of cholestasis.While the diagnosis of such disorders had historically been based on pattern recognition of unremitting cholestasis without other identified molecular or anatomic cause,recent scientific advancements have uncovered multiple specific responsible proteins.The variety of identified defects has resulted in an ever-broadening phenotypic spectrum,ranging from traditional benign recurrent jaundice to progressive cholestasis and end-stage liver disease.AIM To review current data on defects in bile acid homeostasis,explore the expanding knowledge base of genetic based diseases in this field,and report disease characteristics and management.METHODS We conducted a systemic review according to PRISMA guidelines.We performed a Medline/PubMed search in February-March 2019 for relevant articles relating to the understanding,diagnosis,and management of bile acid homeostasis with a focus on the family of diseases collectively known as PFIC.English only articles were accessed in full.The manual search included references of retrieved articles.We extracted data on disease characteristics,associations with other diseases,and treatment.Data was summarized and presented in text,figure,and table format.RESULTS Genetic-based liver disease resulting in the inability to properly form and secrete bile constitute an important cause of morbidity and mortality in children and increasingly in adults.A growing number of PFIC have been described based on an expanded understanding of biliary transport mechanism defects and the development of a common phenotype.CONCLUSION We present a summary of current advances made in a number of areas relevant to both the classically described FIC1(ATP8B1),BSEP(ABCB11),and MDR3(ABCB4)transporter deficiencies,as well as more recently described gene mutations--TJP2(TJP2),FXR(NR1H4),MYO5B(MYO5B),and others which expand the etiology and understanding of PFIC-related cholestatic diseases and bile transport.
