AIM：To make a comprehensive analysis of the potential pathogenic genes related with Leber congenital amaurosis（LCA） in Chinese.METHODS：LCA subjects and their families were retrospectively collected from 2013 to 20...AIM：To make a comprehensive analysis of the potential pathogenic genes related with Leber congenital amaurosis（LCA） in Chinese.METHODS：LCA subjects and their families were retrospectively collected from 2013 to 2015.Firstly,whole-exome sequencing was performed in patients who had underwent gene mutation screening with nothing found,and then homozygous sites was selected,candidate sites were annotated,and pathogenic analysis was conducted using softwares including Sorting Tolerant from Intolerant（SIFT）,Polyphen-2,Mutation assessor,Condel,and Functional Analysis through Hidden Markov Models（FATHMM）.Furthermore,Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of pathogenic genes were performed followed by co-segregation analysis using Fisher exact Test.Sanger sequencing was used to validate single-nucleotide variations（SNVs）.Expanded verification was performed in the rest patients.RESULTS：Totally 51 LCA families with 53 patients and24 family members were recruited.A total of 104 SNVs（66 LCA-related genes and 15 co-segregated genes）were submitted for expand verification.The frequencies of homozygous mutation of KRT12 and CYP1A1 were simultaneously observed in 3 families.Enrichment analysis showed that the potential pathogenic genes were mainly enriched in functions related to cell adhesion,biological adhesion,retinoid metabolic process,and eye development biological adhesion.Additionally,WFS7 and STAU2 had the highest homozygous frequencies.CONCLUSION：LCA is a highly heterogeneous disease.Mutations in KRT12,CVP1A1,WFS1,and STAU2 may be involved in the development of LCA.展开更多
Background： Progressive myoclonus epilepsies （PMEs） conaprise a group of rare genetic disorders characterized by action rnyoclonus, epileptic seizures, and ataxia with progressive neurologic decline. Due to clinica...Background： Progressive myoclonus epilepsies （PMEs） conaprise a group of rare genetic disorders characterized by action rnyoclonus, epileptic seizures, and ataxia with progressive neurologic decline. Due to clinical and genetic heterogeneity of PMEs, it is difficult to decide which genes are affected. The aim of this study was to report an action myoclonus with or without renal failure syndrome （EPM4） fhmily and summarize the clinical and genetic characteristics of all reported EPM4 patients. Meihods： In the present study, targeted next-generation sequencing （NGS） was applied to screen causative genes in a Chinese PME family. The candidaie variant was further confirmed by cosegregation analysis and further functional analysis, including the reverse transcription polymerase chain reaction and Western blot of the proband＇s muscle. Moreovel, literature data on the clinical and mutational features of all reported EPM4 patients were reviewed. Results： The gene analysis revealed a novel homozygous splicing mutation （c.995-1G〉A） of the SCARB2 gene in two brothers. Further functional analysis revealed that this mutation led to loss function of the SCARB2 protein. The classification of the candidate variant, according to the American College of Medical Genetics and Genomics standards and guidelines and functional analysis, was pathogenic. Therefore, these two brothers were finally diagnostically confirmed as EPM4. Conclusions： These present results suggest the potential for targeted NGS to conduct a more rapid and precise diagnosis for PME patients. A literature review revealed that mutations in the different functional domains of SCARB2 appear to be associated with the phenotype of EPM4.展开更多
AIM: To summarize the phenotypes and identify the underlying genetic cause of the fibrillin-1(FBN1) gene responsible for congenital ectopia lentis(EL) in two Chinese families in northern China.METHODS: A detailed fami...AIM: To summarize the phenotypes and identify the underlying genetic cause of the fibrillin-1(FBN1) gene responsible for congenital ectopia lentis(EL) in two Chinese families in northern China.METHODS: A detailed family history and clinical data from all participants were collected by clinical examination. The candidate genes were captured and sequenced by targeted next-generation sequencing, and the results were confirmed by Sanger sequencing. Haplotyping was used to confirm the mutation sequence. Real-time PCR was used to determine the FBN1 messenger ribonucleic acid(m RNA) levels in patients with EL and in unaffected family members.RESULTS: The probands and other patients in the two families were affected with congenital isolated EL. A heterozygous FBN1 mutation in exon 21(c.2420_IVS20-8 del TCTGAAACAins CGAAAG) was identified in FAMILY-1. A heterozygous FBN1 mutation in exon 14(c.1633 C>T, p.R545 C) was identified in FAMILY-2. Each mutation cosegregated with the affected individuals in the family and did not exist in unaffected family members and 200 unrelated normal controls.CONCLUSION: The insertion-deletion mutation(c.2420 IVS20-8 del TCTGAAACA ins CGAAAG) in the FBN1 gene is first identified in isolated EL. The mutation(c.1633 C>T) in the FBN1 gene was a known mutation in EL patient. The variable phenotypes among the patients expand the phenotypic spectrum of EL in a different ethnic background.展开更多
BACKGROUND Leiomyosarcoma of the stomach is extremely rare,and only 13 cases have been reported in the literature.Before the advent of KIT immunohistochemistry,gastrointestinal stromal tumors(GISTs)were misdiagnosed a...BACKGROUND Leiomyosarcoma of the stomach is extremely rare,and only 13 cases have been reported in the literature.Before the advent of KIT immunohistochemistry,gastrointestinal stromal tumors(GISTs)were misdiagnosed as leiomyomas and leiomyosarcomas.Leiomyosarcoma rarely occurs in organs besides the uterus and is rarely located in the stomach.CASE SUMMARY A 57-year-old woman presented with the symptom of melena over a one-month period.She had suffered weight loss,weakness,nausea and vomiting for fifteen days.At a local hospital,computed tomography showed a very large mass in the stomach,and the results of endoscopic examination and histopathological diagnosis were unclear.She received transfusion therapy and was transferred to our hospital.Upon arrival at our hospital,the patient was anemic.She denied any family history and had no specific past history.No signs of pulmonary metastasis were found on chest radiographs.Magnetic resonance imaging and computed tomography confirmed a very large tumor in the stomach,and no visible signs of metastatic disease were found.On October 30,2013,the patient underwent resection of the stomach tumor and did not undergo any adjuvant treatment.The margins were negative and she had an uneventful recovery and was discharged after 12 d.One year after surgery,the patient died at home,and the cause of death were gastrointestinal obstruction and malnutrition.During that time,she was treated with Chinese medicine but the effect was not ideal.Because of gastrointestinal obstruction,the patient did not receive any reexamination.CONCLUSION Surgical resection is the standard treatment for gastric leiomyosarcoma.The diagnosis of this tumor mainly depends on histopathological examination.This case may suggest the aggressive behavior and poor prognosis of this tumor.展开更多
基金Supported by National Natural Science Foundation of China(No.81470642No.81271045)
文摘AIM：To make a comprehensive analysis of the potential pathogenic genes related with Leber congenital amaurosis（LCA） in Chinese.METHODS：LCA subjects and their families were retrospectively collected from 2013 to 2015.Firstly,whole-exome sequencing was performed in patients who had underwent gene mutation screening with nothing found,and then homozygous sites was selected,candidate sites were annotated,and pathogenic analysis was conducted using softwares including Sorting Tolerant from Intolerant（SIFT）,Polyphen-2,Mutation assessor,Condel,and Functional Analysis through Hidden Markov Models（FATHMM）.Furthermore,Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of pathogenic genes were performed followed by co-segregation analysis using Fisher exact Test.Sanger sequencing was used to validate single-nucleotide variations（SNVs）.Expanded verification was performed in the rest patients.RESULTS：Totally 51 LCA families with 53 patients and24 family members were recruited.A total of 104 SNVs（66 LCA-related genes and 15 co-segregated genes）were submitted for expand verification.The frequencies of homozygous mutation of KRT12 and CYP1A1 were simultaneously observed in 3 families.Enrichment analysis showed that the potential pathogenic genes were mainly enriched in functions related to cell adhesion,biological adhesion,retinoid metabolic process,and eye development biological adhesion.Additionally,WFS7 and STAU2 had the highest homozygous frequencies.CONCLUSION：LCA is a highly heterogeneous disease.Mutations in KRT12,CVP1A1,WFS1,and STAU2 may be involved in the development of LCA.
基金This work was supported by the grants from the National Natural Science Foundation of China （No. U1505222, No, 81322017, No. 81500980, and No. 81571100） and the National Key Clinical Specialty Discipline Construction Program and Key Clinical Specialty Discipline Construction Program of Fujian.
文摘Background： Progressive myoclonus epilepsies （PMEs） conaprise a group of rare genetic disorders characterized by action rnyoclonus, epileptic seizures, and ataxia with progressive neurologic decline. Due to clinical and genetic heterogeneity of PMEs, it is difficult to decide which genes are affected. The aim of this study was to report an action myoclonus with or without renal failure syndrome （EPM4） fhmily and summarize the clinical and genetic characteristics of all reported EPM4 patients. Meihods： In the present study, targeted next-generation sequencing （NGS） was applied to screen causative genes in a Chinese PME family. The candidaie variant was further confirmed by cosegregation analysis and further functional analysis, including the reverse transcription polymerase chain reaction and Western blot of the proband＇s muscle. Moreovel, literature data on the clinical and mutational features of all reported EPM4 patients were reviewed. Results： The gene analysis revealed a novel homozygous splicing mutation （c.995-1G〉A） of the SCARB2 gene in two brothers. Further functional analysis revealed that this mutation led to loss function of the SCARB2 protein. The classification of the candidate variant, according to the American College of Medical Genetics and Genomics standards and guidelines and functional analysis, was pathogenic. Therefore, these two brothers were finally diagnostically confirmed as EPM4. Conclusions： These present results suggest the potential for targeted NGS to conduct a more rapid and precise diagnosis for PME patients. A literature review revealed that mutations in the different functional domains of SCARB2 appear to be associated with the phenotype of EPM4.
基金Supported by Natural Science Foundation of Shandong Province (No.ZR2018MH016)China Postdoctoral Science Foundation Funded Project (No.2017M612211)+2 种基金Medical Program of Shandong Province (No.2016WS0265)Qingdao Postdoctoral Application Research Project (No.40518060071)Qingdao Science and Technology Plan (No.16-6-2-14-nsh)
文摘AIM: To summarize the phenotypes and identify the underlying genetic cause of the fibrillin-1(FBN1) gene responsible for congenital ectopia lentis(EL) in two Chinese families in northern China.METHODS: A detailed family history and clinical data from all participants were collected by clinical examination. The candidate genes were captured and sequenced by targeted next-generation sequencing, and the results were confirmed by Sanger sequencing. Haplotyping was used to confirm the mutation sequence. Real-time PCR was used to determine the FBN1 messenger ribonucleic acid(m RNA) levels in patients with EL and in unaffected family members.RESULTS: The probands and other patients in the two families were affected with congenital isolated EL. A heterozygous FBN1 mutation in exon 21(c.2420_IVS20-8 del TCTGAAACAins CGAAAG) was identified in FAMILY-1. A heterozygous FBN1 mutation in exon 14(c.1633 C>T, p.R545 C) was identified in FAMILY-2. Each mutation cosegregated with the affected individuals in the family and did not exist in unaffected family members and 200 unrelated normal controls.CONCLUSION: The insertion-deletion mutation(c.2420 IVS20-8 del TCTGAAACA ins CGAAAG) in the FBN1 gene is first identified in isolated EL. The mutation(c.1633 C>T) in the FBN1 gene was a known mutation in EL patient. The variable phenotypes among the patients expand the phenotypic spectrum of EL in a different ethnic background.
基金Supported by Beijing Municipal Science and Technology Commission,No.Z161100000116045National Natural Science Foundation of China,No.81772642
文摘BACKGROUND Leiomyosarcoma of the stomach is extremely rare,and only 13 cases have been reported in the literature.Before the advent of KIT immunohistochemistry,gastrointestinal stromal tumors(GISTs)were misdiagnosed as leiomyomas and leiomyosarcomas.Leiomyosarcoma rarely occurs in organs besides the uterus and is rarely located in the stomach.CASE SUMMARY A 57-year-old woman presented with the symptom of melena over a one-month period.She had suffered weight loss,weakness,nausea and vomiting for fifteen days.At a local hospital,computed tomography showed a very large mass in the stomach,and the results of endoscopic examination and histopathological diagnosis were unclear.She received transfusion therapy and was transferred to our hospital.Upon arrival at our hospital,the patient was anemic.She denied any family history and had no specific past history.No signs of pulmonary metastasis were found on chest radiographs.Magnetic resonance imaging and computed tomography confirmed a very large tumor in the stomach,and no visible signs of metastatic disease were found.On October 30,2013,the patient underwent resection of the stomach tumor and did not undergo any adjuvant treatment.The margins were negative and she had an uneventful recovery and was discharged after 12 d.One year after surgery,the patient died at home,and the cause of death were gastrointestinal obstruction and malnutrition.During that time,she was treated with Chinese medicine but the effect was not ideal.Because of gastrointestinal obstruction,the patient did not receive any reexamination.CONCLUSION Surgical resection is the standard treatment for gastric leiomyosarcoma.The diagnosis of this tumor mainly depends on histopathological examination.This case may suggest the aggressive behavior and poor prognosis of this tumor.
