title: In search of the DFNA11 myosin VIIA low- and mid-frequency auditory genetic modifier.
abstract: OBJECTIVE
  To evaluate the auditory, vestibular, and retinal characteristics of a large American DFNA11 pedigree with autosomal dominant progressive sensorineural hearing loss that first impacts the low- and mid-frequency auditory range. The pedigree (referred to as the HL2 family) segregates a myosin VIIA (MYO7A) mutation in exon 17 at DNA residue G2164C (MYO7A) that seems to be influenced by a genetic modifier that either rescues or exacerbates the MYO7A alteration. DNA analysis to examine single-nucleotide polymorphisms in 2 candidate modifier genes (ATP2B2 and Wolfram syndrome 1 [WFS1]) is summarized in this report.
  
  
  METHODS
  Family study.
  
  
  RESULTS
  The degree of low- and mid-frequency hearing loss in HL2 family members segregating the MYO7A mutation varies from mild to more severe, with approximately the same number of HL2 family members falling at each end of the severity spectrum. The extent of hearing loss in HL2 individuals can vary between family generations. Differences in the degree of hearing loss in MYO7A HL2 family members may be mirrored by vestibular function in at least 2 of these same individuals. The single-nucleotide polymorphisms examined within ATP2B2 and WFS1 did not segregate with the mild versus more severe auditory phenotype.
  
  
  CONCLUSIONS
  The severity of the auditory and vestibular phenotypes in MYO7A HL2 family members may run in parallel, suggesting a common modifier gene within the inner ear. The putative MYO7A genetic modifier is likely to represent a common polymorphism that is not linked tightly to the MYO7A mutation on the MYO7A allele.
authors.affiliation: V. M. Bloedel Hearing Research Center, Otolaryngology-HNS Department, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Kallman
authors.forename: James O
authors.initials: JO
authors.lastname: Phillips
authors.forename: Naomi F
authors.initials: NF
authors.lastname: Bramhall
authors.forename: John P
authors.initials: JP
authors.lastname: Kelly
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Street
mesh_terms: D002150:Caloric Tests; D022761:Gene Transfer, Horizontal / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics*; D010375:Pedigree; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics; D017354:Point Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012720:Severity of Illness Index; D012737:Sex Factors; D052245:Usher Syndromes / Q000175:diagnosis / Q000235:genetics*; D014929:Wolfram Syndrome / Q000235:genetics
chemical_list: C000631455:MYO7A protein, human; D008565:Membrane Proteins; D000081412:Myosin VIIa; C114987:wolframin protein; D053499:Plasma Membrane Calcium-Transporting ATPases; D009218:Myosins; C506958:ATP2B2 protein, human