Uncovering the CLCN1 Y150* nonsense variant in myotonia congenita: genetic evidence from segregation analysis.

IF 2.1 4区 医学 Q3 CLINICAL NEUROLOGY
Betül Okur Altındaş, Ayse Gul Zamani, Figen Güney, Mahmut Selman Yildirim
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Abstract

Myotonia congenita is a rare genetic disorder characterized by skeletal muscle membrane hyperexcitability due to CLCN1 mutations. It can be inherited in either an autosomal dominant (Thomsen disease) or autosomal recessive (Becker disease) manner. This study describes a homozygous null alteration and its segregation analysis, confirming its pathogenicity. A 30-year-old male, presenting with myotonia since the age of five, was referred to the Medical Genetics clinic. His parents were from the same village, and two of his siblings exhibited similar symptoms. Clinical evaluation was consistent with Becker's myotonia. Next-generation sequencing revealed a homozygous nonsense variant in CLCN1 (NM_000083.2:c.450 C > A, p.Tyr150Ter [Y150*]), which was confirmed by Sanger sequencing in both the proband and his affected brother. This variant has been reported in only five patients. Given that all cases were of Turkish origin and exhibited Becker-type myotonia, our findings support a potential genotype-phenotype association and raise the possibility that this variant may be relatively more prevalent in patients from Türkiye.

发现先天性肌强直clcn1y150 *无义变异:来自分离分析的遗传证据。
先天性肌强直是一种罕见的遗传性疾病,其特征是由CLCN1突变引起的骨骼肌膜亢奋。它可以遗传常染色体显性(Thomsen病)或常染色体隐性(Becker病)方式。本研究描述了一个纯合的零变异及其分离分析,证实了其致病性。一名30岁男性,自5岁起出现肌强直,被转介到医学遗传学诊所。他的父母来自同一个村庄,他的两个兄弟姐妹表现出类似的症状。临床评价与贝克氏肌强直一致。下一代测序显示CLCN1的纯合无义变异(NM_000083.2:c.450)C b> A, p.Tyr150Ter [Y150*]),先证者及其患病兄弟均经Sanger测序证实。据报道,这种变异仅在5例患者中出现。鉴于所有病例均为土耳其裔,并表现出贝克尔型肌强直,我们的研究结果支持潜在的基因型-表型关联,并提出了这种变异在 rkiye患者中相对更普遍的可能性。
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来源期刊
Acta neurologica Belgica
Acta neurologica Belgica 医学-临床神经学
CiteScore
4.20
自引率
3.70%
发文量
300
审稿时长
6-12 weeks
期刊介绍: Peer-reviewed and published quarterly, Acta Neurologica Belgicapresents original articles in the clinical and basic neurosciences, and also reports the proceedings and the abstracts of the scientific meetings of the different partner societies. The contents include commentaries, editorials, review articles, case reports, neuro-images of interest, book reviews and letters to the editor. Acta Neurologica Belgica is the official journal of the following national societies: Belgian Neurological Society Belgian Society for Neuroscience Belgian Society of Clinical Neurophysiology Belgian Pediatric Neurology Society Belgian Study Group of Multiple Sclerosis Belgian Stroke Council Belgian Headache Society Belgian Study Group of Neuropathology
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