Evidence for genotype-phenotype correlation for OTOF mutations

Int J Pediatr Otorhinolaryngol. 2014 Jun;78(6):950-3. doi: 10.1016/j.ijporl.2014.03.022. Epub 2014 Mar 28.

Abstract

Objectives: The aim of this study is to evaluate the auditory phenotype in subjects with OTOF gene mutations to describe genotype-phenotype correlations.

Methods: Twenty-two affected members from three families with homozygous OTOF mutations were included. Nine subjects were evaluated audiologically with otoscopic examination, pure-tone audiometry, tympanometry with acoustic reflex testing, auditory brain stem responses, and otoacoustic emission tests.

Results: Homozygous c.4718T>C (p.Ile1573Thr) mutation was associated with the auditory neuropathy/auditory dys-synchrony (AN/AD) phenotype and with progressive sensorineural hearing loss in four siblings in one family, while homozygous c.4467dupC (p.I1490HfsX19) was associated with severe to profound sensorineural hearing loss without AN/AD in four relatives in another family. Homozygous c.1958delC (p.Pro653LeufsX13) mutation was associated with moderate sensorineural hearing loss without AN/AD in one affected person in an additional family.

Conclusions: The audiological phenotype associated with different OTOF mutations appears to be consistently different suggesting the presence of a genotype-phenotype correlation.

Keywords: Auditory neuropathy; Autosomal recessive; Hearing loss; OTOF.

Publication types

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

MeSH terms

  • Acoustic Impedance Tests
  • Adolescent
  • Adult
  • Audiometry
  • Audiometry, Pure-Tone
  • Child
  • Evoked Potentials, Auditory, Brain Stem
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Mutation*
  • Pedigree
  • Young Adult

Substances

  • Membrane Proteins
  • OTOF protein, human