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. 2021 Oct;185(10):2863-2872.
doi: 10.1002/ajmg.a.62359. Epub 2021 May 29.

Syndromic neurodevelopmental disorder associated with de novo variants in DDX23

William Burns  1 , Lynne M Bird  2   3 , Delphine Heron  4 , Boris Keren  4 , Divya Ramachandra  5 , Isabelle Thiffault  6   7 , Florencia Del Viso  6 , Shivarajan Amudhavalli  8 , Kendra Engleman  8 , Ilaria Parenti  9 , Frank J Kaiser  9 , Jolanta Wierzba  10 , Korbinian M Riedhammer  11   12 , Susanne Liptay  13 , Neda Zadeh  14   15 , Joseph Porrmann  16 , Andrea Fischer  16 , Sophie Gößwein  16 , Heather M McLaughlin  17 , Aida Telegrafi  18 , Katherine G Langley  18 , Richard Steet  1 , Raymond J Louie  1 , Michael J Lyons  1
Affiliations

Syndromic neurodevelopmental disorder associated with de novo variants in DDX23

William Burns et al. Am J Med Genet A. 2021 Oct.

Abstract

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.

Keywords: DDX23; RNA helicase; neurodevelopment.

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