Scholarlink

<p>Mitochondrial diseases are characterized by impaired energy production due to mitochondrial dysfunction. Despite advances in sequencing technologies, many cases remain genetically undiagnosed. We report two cases of mitochondrial disease harboring identical de novo variant in the non-coding RNA gene <i>RNU4-2</i>, previously associated with neurodevelopmental disorders. Re-analysis of whole genome sequencing data from 357 patients ascertained as possibly having mitochondrial disease (see Methods: Supplementary Data <InternalRef RefID="MOESM1">S1</InternalRef>) identified two cases with a pathogenic <i>RNU4-2</i> variant (GRCh38: chr.12:120291839: T &gt; TA; NR_003137.2: n.64_65insT). Both patients exhibited decreased oxygen consumption rates and clinical features including developmental delay, microcephaly, short stature. This study provides the first evidence linking <i>RNU4-2</i> variant to mitochondrial disease, expanding the phenotypic spectrum associated with this gene. Our findings highlight the importance of re-analyzing genomic data and considering non-coding RNA gene variants in mitochondrial disease diagnostics, potentially improving the diagnosis of previously unsolved cases.</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

Identification of a pathogenic RNU4-2 variant in patients with mitochondrial disease: Broadening the spectrum of non-coding RNA gene variants in mitochondrial dysfunction

  • 期刊论文

  • 发表日期：

    2025年7月22日

查看全文
  • Kohta Nakamura,
  • Yoshihito Kishita,
  • Atsuko Imai-Okazaki,
  • Taku Omata,
  • Maki Nodera,
  • Yukiko Yatsuka,
  • Ayumu Sugiura,
  • Naoyuki Matsumoto,
  • Holger Prokisch,
  • Hiroshi Matsumoto,
  • Akira Ohtake,
  • Kei Murayama,
  • Yasushi Okazaki

摘要

Mitochondrial diseases are characterized by impaired energy production due to mitochondrial dysfunction. Despite advances in sequencing technologies, many cases remain genetically undiagnosed. We report two cases of mitochondrial disease harboring identical de novo variant in the non-coding RNA gene RNU4-2, previously associated with neurodevelopmental disorders. Re-analysis of whole genome sequencing data from 357 patients ascertained as possibly having mitochondrial disease (see Methods: Supplementary Data S1) identified two cases with a pathogenic RNU4-2 variant (GRCh38: chr.12:120291839: T > TA; NR_003137.2: n.64_65insT). Both patients exhibited decreased oxygen consumption rates and clinical features including developmental delay, microcephaly, short stature. This study provides the first evidence linking RNU4-2 variant to mitochondrial disease, expanding the phenotypic spectrum associated with this gene. Our findings highlight the importance of re-analyzing genomic data and considering non-coding RNA gene variants in mitochondrial disease diagnostics, potentially improving the diagnosis of previously unsolved cases.