Old gene, new phenotype: splice-altering variants in CEACAM16 cause recessive non-syndromic hearing impairment

Kevin T Booth; Kimia Kahrizi; Hossein Najmabadi; Hela Azaiez; Richard JH Smith

doi:10.1136/jmedgenet-2018-105349

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Old gene, new phenotype: splice-altering variants in CEACAM16 cause recessive non-syndromic hearing impairment

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Old gene, new phenotype: splice-altering variants in CEACAM16 cause recessive non-syndromic hearing impairment

Kevin T Booth, Kimia Kahrizi, Hossein Najmabadi, Hela Azaiez and Richard JH Smith

Journal of medical genetics, Vol.55(8), pp.555-560

08/2018

DOI: 10.1136/jmedgenet-2018-105349

PMID: 29703829

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https://www.ncbi.nlm.nih.gov/pmc/articles/6060001View

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Abstract

BackgroundHearing loss is a genetically and phenotypically heterogeneous disorder.ObjectivesThe purpose of this study was to determine the genetic cause underlying the postlingual progressive hearing loss in two Iranian families.MethodsWe used OtoSCOPE, a next-generation sequencing platform targeting >150 genes causally linked to deafness, to screen two deaf probands. Data analysis was completed using a custom bioinformatics pipeline, and variants were functionally assessed using minigene splicing assays.ResultsWe identified two homozygous splice-altering variants (c.37G>T and c.662–1G>C) in the CEACAM16 gene, segregating with the deafness in each family. The minigene splicing results revealed the c.37G>T results in complete skipping of exon 2 and loss of the AUG start site. The c.662–1G>C activates a cryptic splice site inside exon 5 resulting in a shift in the mRNA reading frame.ConclusionsThese results suggest that loss-of-function mutations in CEACAM16 result in postlingual progressive hearing impairment and further support the role of CEACAM16 in auditory function.

Details

Title: Subtitle: Old gene, new phenotype: splice-altering variants in CEACAM16 cause recessive non-syndromic hearing impairment
Creators: Kevin T Booth - The Interdisciplinary Graduate Program in Molecular Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Kimia Kahrizi - Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Islamic Republic of Iran
Hossein Najmabadi - Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Islamic Republic of Iran
Hela Azaiez - Molecular Otolaryngology Renal Research Laboratories, Department of Otolaryngology, University of Iowa, Iowa City, Iowa, USA
Richard JH Smith - The Interdisciplinary Graduate Program in Molecular Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
Resource Type: Journal article
Publication Details: Journal of medical genetics, Vol.55(8), pp.555-560
DOI: 10.1136/jmedgenet-2018-105349
PMID: 29703829
NLM abbreviation: J Med Genet
ISSN: 0022-2593
eISSN: 1468-6244
Grant note: DOI: 10.13039/501100003968, name: Iranian National Science Foundation; DOI: 10.13039/100000055, name: National Institute on Deafness and Other Communication Disorders
Language: English
Date published: 08/2018
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
Record Identifier: 9984006365402771

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