A genotypic ascertainment approach to refute the association of MYO1A variants with non-syndromic deafness

Eur J Hum Genet. 2016 Jan;25(1):147-149. doi: 10.1038/ejhg.2016.140. Epub 2016 Oct 19.

Abstract

Variants in the unconventional myosin gene, MYO1A, have been reported to cause non-syndromic sensorineural hearing loss with a pattern of autosomal dominant inheritance. Others have challenged this association. We used a genotypic ascertainment study design to test the association of MYO1A variants with hearing loss. We evaluated MYO1A variants from a cohort of 951 individuals with exome sequencing who were not ascertained for hearing loss. Five individuals had one of two variants claimed to be associated with sensorineural hearing loss in a prior study and 33 individuals had one of 13 predicted deleterious variants. We obtained audiology evaluations for 12 individuals with these variants of interest. The hearing acuity of the participants was compared with age- and sex-matched controls and published age- and sex-specific reference ranges from a large population of otologically screened adults. None of the participants had bilateral sensorineural hearing loss of moderate or greater severity. These data do not support a causal relationship of variants in MYO1A to sensorineural hearing loss. We suggest that the genotypic ascertainment method is useful to objectively evaluate gene-phenotype associations.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Exome / genetics
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Hearing Loss / genetics*
  • Hearing Loss / physiopathology
  • Hearing Loss, Sensorineural / genetics*
  • Hearing Loss, Sensorineural / physiopathology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Middle Aged
  • Myosin Heavy Chains / genetics*
  • Myosin Type I / genetics*
  • Pedigree

Substances

  • MYO1A protein, human
  • Myosin Type I
  • Myosin Heavy Chains