Variable hearing impairment in a DFNB2 family with a novel MYO7A missense mutation.
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.
Department of Otolaryngology, University of Iowa, Iowa City, IA, USA.
M S
MS
Hildebrand
N P
NP
Thorne
C J
CJ
Bromhead
K
K
Kahrizi
J A
JA
Webster
Z
Z
Fattahi
M
M
Bataejad
W J
WJ
Kimberling
D
D
Stephan
H
H
Najmabadi
M
M
Bahlo
R J H
RJ
Smith
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D003241:Consanguinity; D005190:Family; D005260:Female; D034381:Hearing Loss / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics*
C000631455:MYO7A protein, human; D000081412:Myosin VIIa; D009218:Myosins