Screening of SLC26A4, FOXI1, KCNJ10, and GJB2 in bilateral deafness patients with inner ear malformation

Otolaryngol Head Neck Surg. 2012 Jun;146(6):972-8. doi: 10.1177/0194599812439670. Epub 2012 Mar 12.

Abstract

Objective: Bilateral nonsyndromic sensorineural hearing loss associated with inner ear malformation is closely related to genetics. SLC26A4 is considered to be the major involved gene. Recently, FOXI1 and KCNJ10 mutations have been linked to enlarged vestibular aqueducts and GJB2 mutations linked to temporal bone malformation. The authors aimed to investigate the mutation spectrums of these genes in Chinese patients with bilateral hearing impairment associated with inner ear malformation.

Study design: Cross-sectional study.

Setting: Affiliated hospital of the university.

Subjects and methods: The authors analyzed the GJB2, SLC26A4, FOXI1, and KCNJ10 gene sequences in 43 patients presenting with bilateral hearing impairment associated with inner ear malformation using pyrosequencing and direct DNA sequencing.

Results: In total, 74.4% (32/43) of patients carried at least 1 of 14 pathogenic SLC26A4 mutations, including 6 novel mutations and 4 polymorphisms. Patients with enlarged vestibular aqueducts had a higher rate of SLC26A4 mutation than Mondini dysplasia patients. No FOXI1 or KCNJ10 potential pathogenic mutation was present, and GJB2 biallelic pathogenic mutations were uncommon (2.3%; 1/43). No significant correlation was observed between the genotype and phenotype of SLC26A4 mutations.

Conclusion: SLC26A4 accounts for 74.4% of inner ear malformations in our cohort, whereas FOXI1, KCNJ10, and GJB2 mutations are not common. Other possible genes or external factors may contribute to this multibranch abnormality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Asian People / genetics
  • Child
  • Child, Preschool
  • China
  • Cohort Studies
  • Connexin 26
  • Connexins / genetics*
  • Deafness / genetics*
  • Ear, Inner / abnormalities*
  • Female
  • Forkhead Transcription Factors / genetics*
  • Hearing Loss, Sensorineural / complications
  • Hearing Loss, Sensorineural / genetics
  • Hearing Loss, Sensorineural / pathology
  • Humans
  • Male
  • Membrane Transport Proteins / genetics*
  • Potassium Channels, Inwardly Rectifying / genetics*
  • Sulfate Transporters
  • Young Adult

Substances

  • Connexins
  • FOXI1 protein, human
  • Forkhead Transcription Factors
  • GJB2 protein, human
  • Kcnj10 (channel)
  • Membrane Transport Proteins
  • Potassium Channels, Inwardly Rectifying
  • SLC26A4 protein, human
  • Sulfate Transporters
  • Connexin 26

Supplementary concepts

  • Nonsyndromic sensorineural hearing loss