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Nonsyndromic hearing loss DFNA10 and a novel mutation of EYA4 : Evidence for correlation of normal cardiac phenotype with truncating mutations of the Eya domain
Author(s) -
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.
Publication year - 2007
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.31793
Subject(s) - hearing loss , frameshift mutation , sensorineural hearing loss , phenotype , genetics , mutation , medicine , dilated cardiomyopathy , allele , audiology , biology , gene , heart failure
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.