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.
AuthorsM S Hildebrand, N P Thorne, C J Bromhead, K Kahrizi, J A Webster, Z Fattahi, M Bataejad, W J Kimberling, D Stephan, H Najmabadi, M Bahlo, R J H Smith
JournalClinical genetics (Clin Genet) Vol. 77 Issue 6 Pg. 563-71 (Jun 2010) ISSN: 1399-0004 [Electronic] Denmark
PMID20132242 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Myosins
  • myosin VIIa
  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Chromosome Mapping
  • Consanguinity
  • Family
  • Female
  • Hearing Loss (genetics)
  • Hearing Loss, Sensorineural (genetics)
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense
  • Myosins (genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: