{"title":"A novel mutation in <i>SETX</i> and <i>ATM</i> causes ataxia in consanguineous Pakistani families.","authors":"Rabia Akram, Shahid Mahmood Baig, Haseeb Anwar, Ghulam Hussain","doi":"10.12669/pjms.40.8.9246","DOIUrl":null,"url":null,"abstract":"<p><strong>Background & objectives: </strong>Ataxia is usually caused by cerebellar pathology or a decrease in vestibular or proprioceptive afferent input to the cerebellum. It is characterized by uncoordinated walking, truncal instability, body or head tremors, uncontrolled coordination of the hands, dysarthria, and aberrant eye movements. The objective of the current investigation was to identify the underlying genetic cause of the hereditary ataxia that affects the Pakistani population.</p><p><strong>Methods: </strong>We studied numerous consanguineous Pakistani families whose members had ataxia-related clinical symptoms to varying degrees. The families were chosen from the Punjab province, and the neurophysician conducted a clinical examination. Peripheral blood samples from both sick and healthy members of the family were taken after obtaining informed consent. Genomic DNA was used to find potential variations in probands using whole exome sequencing. The study was carried out at the University Hospital of Tübingen, Germany, and Government College University in Faisalabad, Pakistan, during 2018-2023.</p><p><strong>Results: </strong>The molecular analysis of these families identified different variants including <i>SGCB</i>: c.902C>T, c.668G>A, <i>ATM</i>: c.6196_6197insGAA, <i>SPG11</i>: c.5769del, <i>SETX</i> c.5525_5533del, and <i>ATM</i>: c.7969A>T. A noteworthy mutation in <i>ATM</i> and <i>SETX</i> was observed among them, and its symptoms were shown to cause ataxia in these families.</p><p><strong>Conclusion: </strong>The current study broadens the mutation spectrum of several hereditary ataxia types and suggests the next generation sequencing in conjunction with clinical research for a more accurate diagnosis of overlapping phenotypes of this disorder in the Pakistani population.</p>","PeriodicalId":19958,"journal":{"name":"Pakistan Journal of Medical Sciences","volume":"40 8","pages":"1765-1769"},"PeriodicalIF":1.2000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11395355/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pakistan Journal of Medical Sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.12669/pjms.40.8.9246","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background & objectives: Ataxia is usually caused by cerebellar pathology or a decrease in vestibular or proprioceptive afferent input to the cerebellum. It is characterized by uncoordinated walking, truncal instability, body or head tremors, uncontrolled coordination of the hands, dysarthria, and aberrant eye movements. The objective of the current investigation was to identify the underlying genetic cause of the hereditary ataxia that affects the Pakistani population.
Methods: We studied numerous consanguineous Pakistani families whose members had ataxia-related clinical symptoms to varying degrees. The families were chosen from the Punjab province, and the neurophysician conducted a clinical examination. Peripheral blood samples from both sick and healthy members of the family were taken after obtaining informed consent. Genomic DNA was used to find potential variations in probands using whole exome sequencing. The study was carried out at the University Hospital of Tübingen, Germany, and Government College University in Faisalabad, Pakistan, during 2018-2023.
Results: The molecular analysis of these families identified different variants including SGCB: c.902C>T, c.668G>A, ATM: c.6196_6197insGAA, SPG11: c.5769del, SETX c.5525_5533del, and ATM: c.7969A>T. A noteworthy mutation in ATM and SETX was observed among them, and its symptoms were shown to cause ataxia in these families.
Conclusion: The current study broadens the mutation spectrum of several hereditary ataxia types and suggests the next generation sequencing in conjunction with clinical research for a more accurate diagnosis of overlapping phenotypes of this disorder in the Pakistani population.
期刊介绍:
It is a peer reviewed medical journal published regularly since 1984. It was previously known as quarterly "SPECIALIST" till December 31st 1999. It publishes original research articles, review articles, current practices, short communications & case reports. It attracts manuscripts not only from within Pakistan but also from over fifty countries from abroad.
Copies of PJMS are sent to all the import medical libraries all over Pakistan and overseas particularly in South East Asia and Asia Pacific besides WHO EMRO Region countries. Eminent members of the medical profession at home and abroad regularly contribute their write-ups, manuscripts in our publications. We pursue an independent editorial policy, which allows an opportunity to the healthcare professionals to express their views without any fear or favour. That is why many opinion makers among the medical and pharmaceutical profession use this publication to communicate their viewpoint.