Scholarlink

<p>Kabuki syndrome type 1 (KS1) is a monogenic disorder arising from pathogenic variants within <i>KMT2D</i> and characterized by syndromic neurodevelopmental delay. We report the retrospective identification of a causative <i>Alu</i>Y insertion within <i>KMT2D</i> in a genetically unsolved individual with typical KS1 features, after identification of a DNA methylation signature. This is the first documentation of <i>Alu</i> insertion as a molecular mechanism responsible for KS1. This study emphasizes the need for reanalyzing inconclusive sequencing data in individuals with gene-specific phenotypes and reinforces episignature as a reliable diagnostic tool when NGS approaches fail to provide conclusive results in individuals with rare diseases.</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

Reverse genotyping: unveiling Alu element insertion as a new cause of Kabuki syndrome using DNA methylation signature

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月29日

查看全文
  • Quentin Sabbagh,
  • Nathalie Ruiz-Pallares,
  • Cassandra Rastin,
  • Jacques Puechberty,
  • Thomas Guignard,
  • Claire Jeandel,
  • Fanny Merklen,
  • Pascal Pujol,
  • Jennifer Kerkhof,
  • Bekim Sadikovic,
  • Mouna Barat-Houari,
  • David Geneviève

摘要

Kabuki syndrome type 1 (KS1) is a monogenic disorder arising from pathogenic variants within KMT2D and characterized by syndromic neurodevelopmental delay. We report the retrospective identification of a causative AluY insertion within KMT2D in a genetically unsolved individual with typical KS1 features, after identification of a DNA methylation signature. This is the first documentation of Alu insertion as a molecular mechanism responsible for KS1. This study emphasizes the need for reanalyzing inconclusive sequencing data in individuals with gene-specific phenotypes and reinforces episignature as a reliable diagnostic tool when NGS approaches fail to provide conclusive results in individuals with rare diseases.