Identification of a novel pathogenic OTOF variant causative of nonsyndromic hearing loss with high frequency in the Ashkenazi Jewish population

Mutations in the OTOF gene have previously been shown to cause nonsyndromic prelingual deafness (DFNB9, OMIM 601071) as well as auditory neuropathy/dys-synchrony. In this study, the OTOF NM_194248.2 c.5332G>T, p.Val1778Phe variant was identified in a large Ashkenazi Jewish family as the causative...

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Bibliographic Details
Published in:Application of clinical genetics 2016-01, Vol.9, p.141-146
Main Authors: Fedick, Anastasia M, Jalas, Chaim, Swaroop, Ananya, Smouha, Eric E, Webb, Bryn D
Format: Article
Language:English
Subjects:
Analysis
Ashkenazi Jewish
Audiology
c.5332G>T
Consent
Deafness
Families & family life
Females
Genetic aspects
Genotype & phenotype
Hair
Hearing aids
Hearing loss
Hearing protection
Jewish people
Mutation
Original Research
OTOF
p.Val1778Phe
Patients
Population
Proteins
Siblings
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Summary:Mutations in the OTOF gene have previously been shown to cause nonsyndromic prelingual deafness (DFNB9, OMIM 601071) as well as auditory neuropathy/dys-synchrony. In this study, the OTOF NM_194248.2 c.5332G>T, p.Val1778Phe variant was identified in a large Ashkenazi Jewish family as the causative variant in four siblings with hearing loss. Our analysis reveals a carrier frequency of the OTOF c.5332G>T, p.Val1778Phe variant of 1.27% in the Ashkenazi Jewish population, suggesting that this variant may be a significant contributor to nonsyndromic sensorineural hearing loss and should be considered for inclusion in targeted hearing loss panels for this population. Of note, the degree of hearing loss associated with this phenotype ranged from mild to moderately severe, with two of the four siblings not known to have hearing loss until they were genotyped and underwent pure tone audiometry and auditory brainstem response testing. The phenotypic variability along with the auditory neuropathy/dys-synchrony, which allows for the production of otoacoustic emissions, supports that nonsyndromic hearing loss caused by OTOF mutations may be much more common in the Ashkenazi Jewish population than currently appreciated due to a lack of diagnosis.
ISSN:1178-704X
1178-704X
DOI:10.2147/TACG.S113828