Angela Krutish, James Elmore, Werner Ilse, Janine L Johnston, Dustin Hittel, Marina Kerr, Aneal Khan, Cheryl Rockman-Greenberg, Aizeddin A Mhanni
{"title":"与孤立性先天性白内障相关的一种新的WFS1变异。","authors":"Angela Krutish, James Elmore, Werner Ilse, Janine L Johnston, Dustin Hittel, Marina Kerr, Aneal Khan, Cheryl Rockman-Greenberg, Aizeddin A Mhanni","doi":"10.1101/mcs.a006259","DOIUrl":null,"url":null,"abstract":"<p><p>Biallelic variants in the <i>WFS1</i> gene are associated with Wolfram syndrome. However, recent publications document that heterozygous variants can lead to a variety of phenotypes, such as Wolfram-like syndrome or isolated features of Wolfram syndrome. In this case report, we present a male patient with a history of congenital cataracts and subjective complaints of muscle weakness. Clinical assessment demonstrated normal muscle strength, and genomic, biochemical, electrophysiologic, and muscle biopsy studies did not identify a potential cause of the proband's perceived muscle weakness. Whole-exome sequencing identified a novel de novo variant in the <i>WFS1</i> gene (c.1243G > T), representing one of only several patients in the published literature with isolated congenital cataracts and a heterozygous <i>WFS1</i> variant. The variety of phenotypes associated with heterozygous variants in <i>WFS1</i> suggests that this gene should be considered as a cause of both dominant and biallelic/recessive forms of disease. Future research should focus on elucidating the mechanism(s) of disease and variable expressivity in <i>WFS1</i> in order to improve our ability to provide patients and families with anticipatory guidance about the disease, including appropriate screening and medical interventions.</p>","PeriodicalId":10360,"journal":{"name":"Cold Spring Harbor Molecular Case Studies","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/49/da/MCS006259Kru.PMC10111794.pdf","citationCount":"0","resultStr":"{\"title\":\"A novel <i>WFS1</i> variant associated with isolated congenital cataracts.\",\"authors\":\"Angela Krutish, James Elmore, Werner Ilse, Janine L Johnston, Dustin Hittel, Marina Kerr, Aneal Khan, Cheryl Rockman-Greenberg, Aizeddin A Mhanni\",\"doi\":\"10.1101/mcs.a006259\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Biallelic variants in the <i>WFS1</i> gene are associated with Wolfram syndrome. However, recent publications document that heterozygous variants can lead to a variety of phenotypes, such as Wolfram-like syndrome or isolated features of Wolfram syndrome. In this case report, we present a male patient with a history of congenital cataracts and subjective complaints of muscle weakness. Clinical assessment demonstrated normal muscle strength, and genomic, biochemical, electrophysiologic, and muscle biopsy studies did not identify a potential cause of the proband's perceived muscle weakness. Whole-exome sequencing identified a novel de novo variant in the <i>WFS1</i> gene (c.1243G > T), representing one of only several patients in the published literature with isolated congenital cataracts and a heterozygous <i>WFS1</i> variant. The variety of phenotypes associated with heterozygous variants in <i>WFS1</i> suggests that this gene should be considered as a cause of both dominant and biallelic/recessive forms of disease. Future research should focus on elucidating the mechanism(s) of disease and variable expressivity in <i>WFS1</i> in order to improve our ability to provide patients and families with anticipatory guidance about the disease, including appropriate screening and medical interventions.</p>\",\"PeriodicalId\":10360,\"journal\":{\"name\":\"Cold Spring Harbor Molecular Case Studies\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2023-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/49/da/MCS006259Kru.PMC10111794.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cold Spring Harbor Molecular Case Studies\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1101/mcs.a006259\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cold Spring Harbor Molecular Case Studies","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/mcs.a006259","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
A novel WFS1 variant associated with isolated congenital cataracts.
Biallelic variants in the WFS1 gene are associated with Wolfram syndrome. However, recent publications document that heterozygous variants can lead to a variety of phenotypes, such as Wolfram-like syndrome or isolated features of Wolfram syndrome. In this case report, we present a male patient with a history of congenital cataracts and subjective complaints of muscle weakness. Clinical assessment demonstrated normal muscle strength, and genomic, biochemical, electrophysiologic, and muscle biopsy studies did not identify a potential cause of the proband's perceived muscle weakness. Whole-exome sequencing identified a novel de novo variant in the WFS1 gene (c.1243G > T), representing one of only several patients in the published literature with isolated congenital cataracts and a heterozygous WFS1 variant. The variety of phenotypes associated with heterozygous variants in WFS1 suggests that this gene should be considered as a cause of both dominant and biallelic/recessive forms of disease. Future research should focus on elucidating the mechanism(s) of disease and variable expressivity in WFS1 in order to improve our ability to provide patients and families with anticipatory guidance about the disease, including appropriate screening and medical interventions.
期刊介绍:
Cold Spring Harbor Molecular Case Studies is an open-access, peer-reviewed, international journal in the field of precision medicine. Articles in the journal present genomic and molecular analyses of individuals or cohorts alongside their clinical presentations and phenotypic information. The journal''s purpose is to rapidly share insights into disease development and treatment gained by application of genomics, proteomics, metabolomics, biomarker analysis, and other approaches. The journal covers the fields of cancer, complex diseases, monogenic disorders, neurological conditions, orphan diseases, infectious disease, gene therapy, and pharmacogenomics. It has a rapid peer-review process that is based on technical evaluation of the analyses performed, not the novelty of findings, and offers a swift, clear path to publication. The journal publishes: Research Reports presenting detailed case studies of individuals and small cohorts, Research Articles describing more extensive work using larger cohorts and/or functional analyses, Rapid Communications presenting the discovery of a novel variant and/or novel phenotype associated with a known disease gene, Rapid Cancer Communications presenting the discovery of a novel variant or combination of variants in a cancer type, Variant Discrepancy Resolution describing efforts to resolve differences or update variant interpretations in ClinVar through case-level data sharing, Follow-up Reports linked to previous observations, Plus Review Articles, Editorials, and Position Statements on best practices for research in precision medicine.