Scholarlink

<p>Limb-girdle muscular dystrophy type 1B is one of several muscular dystrophies caused by pathogenic variants in the <i>LMNA</i> gene. In this study, we investigated the clinical, pathological, and genetic findings of an LGMD1B family. Genetic sequencing identified the proband and her younger brother both carried the canonical splicing c.513 + 1G &gt; A variant in the <i>LMNA</i> gene. The variant was absent in the proband’s mother, and a certain percentage of the <i>LMNA</i> variant was identified in the venous blood, urine, and semen sample of the proband’s father by pyrophosphate sequencing. Further cDNA analysis demonstrated that the canonical splicing c.513 + 1G &gt; A variant in intron 2 induced retention of the first 45&#xa0;bp of intron 2, resulting in an in-frame insertion of 15 amino acids. Our study directly confirmed the presence of somatic and germinal mosaicism in the LGMD1B family and the pathogenicity of the canonical splicing variant in the <i>LMNA</i> gene.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Somatic and germinal mosaicism of a canonical splicing variant causing limb-girdle muscular dystrophy type 1B

  • 期刊论文

  • 发表日期：

    2025年8月16日

查看全文
  • Guangyu Wang,
  • Yaru Wang,
  • Dandan Zhao,
  • Chuanzhu Yan,
  • Pengfei Lin

摘要

Limb-girdle muscular dystrophy type 1B is one of several muscular dystrophies caused by pathogenic variants in the LMNA gene. In this study, we investigated the clinical, pathological, and genetic findings of an LGMD1B family. Genetic sequencing identified the proband and her younger brother both carried the canonical splicing c.513 + 1G > A variant in the LMNA gene. The variant was absent in the proband’s mother, and a certain percentage of the LMNA variant was identified in the venous blood, urine, and semen sample of the proband’s father by pyrophosphate sequencing. Further cDNA analysis demonstrated that the canonical splicing c.513 + 1G > A variant in intron 2 induced retention of the first 45 bp of intron 2, resulting in an in-frame insertion of 15 amino acids. Our study directly confirmed the presence of somatic and germinal mosaicism in the LGMD1B family and the pathogenicity of the canonical splicing variant in the LMNA gene.