{"title":"SETX和ATM的新型突变会导致巴基斯坦近亲家庭出现共济失调。","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":"{\"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}","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
摘要
背景和目的:共济失调通常是由小脑病变或小脑前庭或本体感觉传入减少引起的。共济失调的特征是行走不协调、躯干不稳定、身体或头部震颤、双手协调失控、构音障碍和眼球运动失常。本次调查的目的是找出影响巴基斯坦人群的遗传性共济失调的潜在遗传原因:我们研究了许多巴基斯坦近亲家庭,这些家庭的成员都有不同程度的共济失调相关临床症状。这些家庭选自旁遮普省,由神经物理学家进行临床检查。在获得知情同意后,采集了患病和健康家庭成员的外周血样本。使用基因组 DNA 进行全外显子测序,以发现潜在的变异。研究于 2018-2023 年期间在德国图宾根大学医院和巴基斯坦费萨拉巴德政府学院大学进行:对这些家族的分子分析发现了不同的变异,包括SGCB:c.902C>T、c.668G>A、ATM:c.6196_6197insGAA、SPG11:c.5769del、SETX c.5525_5533del和ATM:c.7969A>T。其中值得注意的是ATM和SETX的突变,其症状被证明会导致这些家庭出现共济失调:目前的研究拓宽了几种遗传性共济失调类型的突变谱,并建议将下一代测序与临床研究相结合,以更准确地诊断巴基斯坦人群中这种疾病的重叠表型。
A novel mutation in SETX and ATM causes ataxia in consanguineous Pakistani families.
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.