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Syndromic neurodevelopmental disorder associated with de novo variants in DDX23
Author(s) -
Burns William,
Bird Lynne M.,
Heron Delphine,
Keren Boris,
Ramachandra Divya,
Thiffault Isabelle,
Del Viso Florencia,
Amudhavalli Shivarajan,
Engleman Kendra,
Parenti Ilaria,
Kaiser Frank J.,
Wierzba Jolanta,
Riedhammer Korbinian M.,
Liptay Susanne,
Zadeh Neda,
Porrmann Joseph,
Fischer Andrea,
Gößwein Sophie,
McLaughlin Heather M.,
Telegrafi Aida,
Langley Katherine G.,
Steet Richard,
Louie Raymond J.,
Lyons Michael J.
Publication year - 2021
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.62359
Subject(s) - missense mutation , rna splicing , biology , genetics , neurodevelopmental disorder , rna helicase a , autism , rna , helicase , autism spectrum disorder , alternative splicing , rna binding protein , gene , mutation , medicine , messenger rna , psychiatry
The DEAD/DEAH box RNA helicases are a superfamily of proteins involved in the processing and transportation of RNA within the cell. A growing literature supports this family of proteins as contributing to various types of human disorders from neurodevelopmental disorders to syndromes with multiple congenital anomalies. This article presents a cohort of nine unrelated individuals with de novo missense alterations in DDX23 (Dead‐Box Helicase 23). The gene is ubiquitously expressed and functions in RNA splicing, maintenance of genome stability, and the sensing of double‐stranded RNA. Our cohort of patients, gathered through GeneMatcher, exhibited features including tone abnormalities, global developmental delay, facial dysmorphism, autism spectrum disorder, and seizures. Additionally, there were a variety of other findings in the skeletal, renal, ocular, and cardiac systems. The missense alterations all occurred within a highly conserved RecA‐like domain of the protein, and are located within or proximal to the DEAD box sequence. The individuals presented in this article provide evidence of a syndrome related to alterations in DDX23 characterized predominantly by atypical neurodevelopment.