title: Nonsyndromic hearing loss DFNA10 and a novel mutation of EYA4: evidence for correlation of normal cardiac phenotype with truncating mutations of the Eya domain.
abstract: 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, 1,490insAA, of EYA4. The 1,490insAA 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.
authors.affiliation: Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville 20850-3320, Maryland, USA.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Makishima
authors.forename: Anne C
authors.initials: AC
authors.lastname: Madeo
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Brewer
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Zalewski
authors.forename: John A
authors.initials: JA
authors.lastname: Butman
authors.forename: Vandana
authors.initials: V
authors.lastname: Sachdev
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Arai
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Holbrook
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Rosing
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Griffith
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D004252:DNA Mutational Analysis; D004452:Echocardiography; D004562:Electrocardiography; D005192:Family Health; D005260:Female; D016368:Frameshift Mutation; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D015534:Trans-Activators / Q000235:genetics*
chemical_list: C117736:EYA4 protein, human; D015534:Trans-Activators