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<p>Myotonia congenita is a rare genetic disorder characterized by skeletal muscle membrane hyperexcitability due to <i>CLCN1</i> 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 <i>CLCN1</i> (<i>NM_000083.2</i>:c.450&#xa0;C &gt; 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.</p>

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

  • 期刊论文

  • 发表日期：

    2025年8月9日

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  • Betül Okur Altındaş,
  • Ayse Gul Zamani,
  • Figen Güney,
  • Mahmut Selman Yildirim

摘要

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.