Nonsyndromic hearing loss DFNA10 and a novel mutation of EYA4: Evidence for correlation of normal cardiac phenotype with truncating mutations of the Eya domain

Dominant, truncating mutations of eyes absent 4 (EYA4) on chromosome 6q23 can cause either nonsyndromic hearing loss DFNA10 or hearing loss with dilated cardiomyopathy (DCM). It has been proposed that truncations of the C‐terminal Eya domain cause DFNA10 whereas upstream truncations of the N‐termina...

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Bibliographic Details
Published in:American journal of medical genetics. Part A 2007-07, Vol.143A (14), p.1592-1598
Main Authors: Makishima, Tomoko, Madeo, Anne C., Brewer, Carmen C., Zalewski, Christopher K., Butman, John A., Sachdev, Vandana, Arai, Andrew E., Holbrook, Brenda M., Rosing, Douglas R., Griffith, Andrew J.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Base Sequence
Binding Sites - genetics
cardiomyopathy
deafness
DNA Mutational Analysis
ear
Echocardiography
Electrocardiography
EYA4
Family Health
Female
Frameshift Mutation
Genotype
hearing
hearing loss
Hearing Loss - genetics
Hearing Loss - pathology
Hearing Loss - physiopathology
Heart - physiopathology
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Pedigree
Phenotype
Trans-Activators - genetics
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Summary:Dominant, truncating mutations of eyes absent 4 (EYA4) on chromosome 6q23 can cause either nonsyndromic hearing loss DFNA10 or hearing loss with dilated cardiomyopathy (DCM). It has been proposed that truncations of the C‐terminal Eya domain cause DFNA10 whereas upstream truncations of the N‐terminal variable region cause hearing loss with DCM. Here we report an extended family co‐segregating autosomal dominant, postlingual‐onset, progressive, sensorineural hearing loss (SNHL) with a novel frameshift mutation, 1490insAA, of EYA4. The 1490insAA allele is predicted to encode a truncated protein with an intact N‐terminal variable region, but lacking the entire C‐terminal Eya domain. Clinical studies including electrocardiography, echocardiography, and magnetic resonance imaging (MRI) of the heart in nine affected family members revealed no DCM or associated abnormalities and confirmed their nonsyndromic phenotype. These are the first definitive cardiac evaluations of DFNA10 hearing loss to support a correlation of EYA4 mutation position with the presence or absence of DCM. These results will facilitate the counseling of patients with these phenotypes and EYA4 mutations. Published 2007 Wiley‐Liss, Inc.
ISSN:1552-4825
1552-4833
DOI:10.1002/ajmg.a.31793