{"title":"A case report of oculopharyngodistal myopathy with 126 CGG repeat expansions in <i>RILPL1</i>.","authors":"Wenjing Wang, Tielun Yin, Xinyu Zhang, Zhaoxia Wang, Tianyun Wang, Shuo Zhang, Yingshuang Zhang, Dongsheng Fan","doi":"10.3389/fgene.2025.1472907","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Oculopharyngodistal myopathy (OPDM) is a rare hereditary muscle disease characterized by progressive ptosis, ophthalmoplegia, dysphagia, dysarthria, and distal muscle weakness. The genetic basis was identified in 2019 with CGG repeat expansions in the noncoding region of <i>LRP12</i>. Similar expansions in <i>GIPC1, NOTCH2NLC, and RILPL1</i> were later linked to OPDM, classifying the disease into OPDM1-4. OPDM4, associated with <i>RILPL1</i>, was discovered in 2022 with a few confirmed cases worldwide, leaving its clinical features and pathogenic mechanisms largely unexplored.</p><p><strong>Case presentation: </strong>We present a patient with OPDM4 who had suffered progressive ptosis, external ophthalmoplegia, pharyngeal weakness, facial muscle weakness, and distal limb weakness over the past 20 years. Electromyography (EMG) revealed myogenic damage and normal H-reflex latency. A biopsy of the left biceps brachii revealed myogenic changes with atypical rimmed vacuoles in some muscle fibers. Screening for extra-muscular system involvement revealed no obvious involvement of the heart or central nervous system. Genetic analysis confirmed 126 CGG repeat expansions in <i>RILPL1</i> and excluded abnormal CGG repeat expansions in <i>LRP12, GIPC1, and NOTCH2NLC</i>.</p><p><strong>Conclusion: </strong>This case broadens the spectrum of CGG repeat numbers in the <i>RILPL1</i> gene associated with OPDM4. In addition, systematic medical examinations revealed several new characteristics of OPDM4, which have not been reported previously, such as normal H reflex, potential mild cognitive impairment, etc. These findings expand our knowledge of the phenotypic spectrum of diseases caused by repeat CGG expansions in <i>RILPL1</i>.</p>","PeriodicalId":12750,"journal":{"name":"Frontiers in Genetics","volume":"16 ","pages":"1472907"},"PeriodicalIF":2.8000,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903759/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3389/fgene.2025.1472907","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Oculopharyngodistal myopathy (OPDM) is a rare hereditary muscle disease characterized by progressive ptosis, ophthalmoplegia, dysphagia, dysarthria, and distal muscle weakness. The genetic basis was identified in 2019 with CGG repeat expansions in the noncoding region of LRP12. Similar expansions in GIPC1, NOTCH2NLC, and RILPL1 were later linked to OPDM, classifying the disease into OPDM1-4. OPDM4, associated with RILPL1, was discovered in 2022 with a few confirmed cases worldwide, leaving its clinical features and pathogenic mechanisms largely unexplored.
Case presentation: We present a patient with OPDM4 who had suffered progressive ptosis, external ophthalmoplegia, pharyngeal weakness, facial muscle weakness, and distal limb weakness over the past 20 years. Electromyography (EMG) revealed myogenic damage and normal H-reflex latency. A biopsy of the left biceps brachii revealed myogenic changes with atypical rimmed vacuoles in some muscle fibers. Screening for extra-muscular system involvement revealed no obvious involvement of the heart or central nervous system. Genetic analysis confirmed 126 CGG repeat expansions in RILPL1 and excluded abnormal CGG repeat expansions in LRP12, GIPC1, and NOTCH2NLC.
Conclusion: This case broadens the spectrum of CGG repeat numbers in the RILPL1 gene associated with OPDM4. In addition, systematic medical examinations revealed several new characteristics of OPDM4, which have not been reported previously, such as normal H reflex, potential mild cognitive impairment, etc. These findings expand our knowledge of the phenotypic spectrum of diseases caused by repeat CGG expansions in RILPL1.
Frontiers in GeneticsBiochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
5.50
自引率
8.10%
发文量
3491
审稿时长
14 weeks
期刊介绍:
Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public.
The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.