Pathogenic heterozygous variants in DHX16 have been recently identified in association with a variety of clinical features, including neuromuscular disease, sensorineural hearing loss, ocular anomalies, and other phenotypes. All DHX16 disease-causing variants previously reported in affected individuals are missense in nature, nearly all of which were found to be de novo. Here we report on a patient with neuromuscular disease, hearing loss, retinal degeneration, and previously unreported phenotypic features including mitochondrial deficiency and primary ovarian insufficiency, in whom a novel de novo likely pathogenic variant in DHX16 NM_003587.4:c.2033A > G (p.Glu678Gly) was identified. Furthermore, we conducted an in-depth literature review of DHX16's role in disease and utilized high-performing in silico prediction algorithms to compare and contrast the predicted effects of all reported disease-associated DHX16 variants on protein structure and function.
Keywords: DHX16; NMOAS; hearing loss; neuromuscular disease; primary ovarian insufficiency; retinal degeneration.
© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.