A Frameshift Variant in ANKRD24 Implicates Its Role in Human Non-Syndromic Hearing Loss.

Autor: Kazemi N; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Rezvani Rezvandeh R; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Zare Ashrafi F; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Shokouhian E; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Edizadeh M; Department of Bioinformatics, Genoks Genetic Diagnosis Center, Ankara, Turkey.; Ilyome Bioinformatics, Ankara, Turkey., Booth KTA; Department of Medical & Molecular Genetics, Indiana University, Indianapolis, Indiana, USA.; Department of Otolaryngology, Head & Neck Surgery, Indiana University, Indianapolis, Indiana, USA., Kahrizi K; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Najmabadi H; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran., Mohseni M; Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2024 Oct 21. Date of Electronic Publication: 2024 Oct 21.
DOI: 10.1111/cge.14635
Abstrakt: Hearing loss (HL) is the most prevalent sensorineural disorders, affecting about one in 1000 newborns. Over half of the cases are attributed to genetic factors; however, due to the extensive clinical and genetic heterogeneity, many cases remain without a conclusive genetic diagnosis. The advent of next-generation sequencing methodologies in recent years has greatly helped unravel the genetic etiology of HL by identifying numerous genes and causative variants. Despite this, much remains to be uncovered about the genetic basis of sensorineural hearing loss (SNHL). Here, we report an Iranian consanguineous family with postlingual, moderate-to-severe autosomal recessive SNHL. After first excluding plausible variants in known deafness-causing genes using whole exome sequencing, we reanalyzed the data, using a gene/variant prioritization pipeline established for novel gene discovery for HL. This approach identified a novel homozygous frameshift variant c.1934_1937del; (p.Thr645Lysfs*52) in ANKRD24, which segregated with the HL phenotype in the family. Recently, ANKRD24 has been shown to be a pivotal constituent of the stereocilia rootlet in cochlea hair cells and interacts with TRIOBP, a protein already implicated in human deafness. Our data implicate for the first time, ANKRD24 in human nonsyndromic HL (NSHL) and expands the genetic spectrum of HL.
(© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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