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Variable hearing impairment in a DFNB2 family with a novel MYO7A missense mutation


Hildebrand, MS; Thorne, NP; Bromhead, CJ; Kahrizi, K; Webster, JA; Fattahi, Z; Bataejad, M; Kimberling, WJ; Stephan, D; Najmabadi, H; Bahlo, M; Smith, RJH
2010-06
CLINICAL GENETICS
Journal Article
77
6
563-571
Myosin VIIA mutations have been associated with non-syndromic hearing loss (DFNB2; DFNA11) and Usher syndrome type 1B (USH1B). We report clinical and genetic analyses of a consanguineous Iranian family segregating autosomal recessive non-syndromic hearing loss (ARNSHL). The hearing impairment was mapped to the DFNB2 locus using Affymetrix 50K GeneChips; direct sequencing of the MYO7A gene was completed. The Iranian family (L-1419) was shown to segregate a novel homozygous missense mutation (c.1184G>A) that results in a p.R395H amino acid substitution in the motor domain of the myosin VIIA protein. As one affected family member had significantly less severe hearing loss, we used a candidate approach to search for a genetic modifier. This novel MYO7A mutation is the first reported to cause DFNB2 in the Iranian population and this DFNB2 family is the first to be associated with a potential modifier. The absence of vestibular and retinal defects, and less severe low frequency hearing loss, is consistent with the phenotype of a recently reported Pakistani DFNB2 family. Thus, we conclude this family has non-syndromic hearing loss (DFNB2) rather than USH1B, providing further evidence that these two diseases represent discrete disorders.
WILEY-BLACKWELL
MYOSIN-VIIA GENE; LOW-FREQUENCY; INBREEDING COEFFICIENT; RECESSIVE DEAFNESS; MOTOR DOMAIN; MODIFIER; HARMONIN; PROTEIN; DFNA11; IDENTIFICATION
10.1111/j.1399-0004.2009.01344.x
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Creation Date 2010-06-01 12:00:00