Scholarlink

<p>Biallelic pathogenic variants in the <i>MYPN</i> gene are a known cause of congenital myopathy, and exonic variants that activate cryptic splice sites have not been previously reported. Here, we report a Chinese proband with congenital myopathy carrying a homozygous nonsense variant, c.2986C&gt;T (p.Arg996Ter), in exon 14 of the <i>MYPN</i> gene. Transcriptional analysis suggested that this variant likely activated a cryptic donor splice site, truncating the last 91 nucleotides of exon 14 during pre-mRNA splicing. Western blotting and immunofluorescence confirmed a deficiency of myopalladin protein in the proband’s skeletal muscle. Our study highlights that exonic variants, particularly those distant from exon-intron junctions, can induce aberrant pre-mRNA splicing. This insight is crucial for interpreting the pathogenicity of variants of uncertain significance and enhancing diagnostic yield in genetic testing.</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

Activation of cryptic donor splice site due to an exonic MYPN variant in congenital myopathy

  • 期刊论文

  • 发表日期：

    2026年6月29日

查看全文
  • Guangyu Wang,
  • Guiguan Yang,
  • Yaru Wang,
  • Chuanzhu Yan,
  • Pengfei Lin

摘要

Biallelic pathogenic variants in the MYPN gene are a known cause of congenital myopathy, and exonic variants that activate cryptic splice sites have not been previously reported. Here, we report a Chinese proband with congenital myopathy carrying a homozygous nonsense variant, c.2986C>T (p.Arg996Ter), in exon 14 of the MYPN gene. Transcriptional analysis suggested that this variant likely activated a cryptic donor splice site, truncating the last 91 nucleotides of exon 14 during pre-mRNA splicing. Western blotting and immunofluorescence confirmed a deficiency of myopalladin protein in the proband’s skeletal muscle. Our study highlights that exonic variants, particularly those distant from exon-intron junctions, can induce aberrant pre-mRNA splicing. This insight is crucial for interpreting the pathogenicity of variants of uncertain significance and enhancing diagnostic yield in genetic testing.