Scholarlink

<p>Colobomatous microphthalmia is a potentially blinding congenital ocular malformation that can present either in isolation or together with other syndromic features. Despite a strong genetic component to disease, many cases lack a molecular diagnosis. We describe an autosomal dominant oculo-vertebral-renal (OVR) syndrome in six independent families characterized by colobomatous microphthalmia, missing vertebrae and congenital kidney abnormalities. Genome sequencing identified six rare variants in the orphan nuclear receptor gene <i>NR6A1</i> in these families. We performed in silico, cellular, and zebrafish experiments to demonstrate the <i>NR6A1</i> variants were pathogenic or likely pathogenic for OVR syndrome. Knockdown of either or both zebrafish paralogs of <i>NR6A1</i> results in abnormal eye, kidney, and somite development, which was rescued by wild-type but not variant <i>NR6A1</i> mRNA. Illustrating the power of genomic ascertainment in medicine, our study establishes <i>NR6A1</i> as a critical factor in eye, kidney, and vertebral development, and a pleiotropic gene responsible for OVR syndrome.</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

Variants in NR6A1 cause a novel oculo vertebral renal syndrome

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月3日

查看全文
  • Uma M. Neelathi,
  • Ehsan Ullah,
  • Aman George,
  • Mara I. Maftei,
  • Elangovan Boobalan,
  • Daniel Sanchez-Mendoza,
  • Chloe Adams,
  • David McGaughey,
  • Yuri V. Sergeev,
  • Ranya AI Rawi,
  • Amelia Naik,
  • Chelsea Bender,
  • Irene H. Maumenee,
  • Michel Michaelides,
  • Tun Giap Tan,
  • Siying Lin,
  • Rafael Villasmil,
  • Delphine Blain,
  • Robert B. Hufnagel,
  • Gavin Arno,
  • Rodrigo M. Young,
  • Bin Guan,
  • Brian P. Brooks

摘要

Colobomatous microphthalmia is a potentially blinding congenital ocular malformation that can present either in isolation or together with other syndromic features. Despite a strong genetic component to disease, many cases lack a molecular diagnosis. We describe an autosomal dominant oculo-vertebral-renal (OVR) syndrome in six independent families characterized by colobomatous microphthalmia, missing vertebrae and congenital kidney abnormalities. Genome sequencing identified six rare variants in the orphan nuclear receptor gene NR6A1 in these families. We performed in silico, cellular, and zebrafish experiments to demonstrate the NR6A1 variants were pathogenic or likely pathogenic for OVR syndrome. Knockdown of either or both zebrafish paralogs of NR6A1 results in abnormal eye, kidney, and somite development, which was rescued by wild-type but not variant NR6A1 mRNA. Illustrating the power of genomic ascertainment in medicine, our study establishes NR6A1 as a critical factor in eye, kidney, and vertebral development, and a pleiotropic gene responsible for OVR syndrome.