A De Novo DHX16 Variant Associated With Neuromuscular Oculoauditory Syndrome Regulates Pre-mRNA Splicing In Vitro.

Authors

Yue Shen, Yunyu Zhou, Chao Lu, Zongfu Cao, Yufei Yu, Tingting Cheng, Huafang Gao, Minna Luo, Xu Ma, Ruifang Sui

Published in

Clinical genetics. Aug 06, 2026. Epub Aug 06, 2026.

Abstract

Neuromuscular oculoauditory syndrome (NMOAS; OMIM# 618733) is a rare neurodevelopmental disorder caused by heterozygous variants in DHX16, a gene in the DExD/H-box RNA helicase family. Despite increasing reports of DHX16-related NMOAS, the functional impact of specific variants on RNA splicing remains poorly understood. In this study, whole-exome sequencing identified a de novo DHX16 variant (c.1360C>G, p.Arg454Gly) in a 2-year-old boy with NMOAS. In vitro assays revealed aberrant intron retention in HSPH1 and FOS transcripts in cells expressing the mutant DHX16-1360G, suggesting impaired splicing efficiency. Longitudinal clinical follow-up uncovered progressive multisystem involvement, including delayed gonadal development and autism spectrum disorder phenotypes not previously linked to DHX16. These findings expand the genotypic and phenotypic spectrum of NMOAS, confirm the pathogenic role of this variant in splicing dysregulation, and emphasize the need for long-term monitoring of emerging comorbidities in affected patients.

PMID:
42562406
Bibliographic data and abstract were imported from PubMed on 07 Aug 2026.

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