A new autosomal-dominant locus (DFNA12) is responsible for a nonsyndromic, midfrequency, prelingual and nonprogressive sensorineural hearing loss

Am J Otol. 1998 Nov;19(6):718-23.

Abstract

Objective: This study aimed to report on the audiologic findings of a nonsyndromic autosomal-dominant hearing loss of which the gene (DFNA 12) recently was found to map to chromosome 11q22-24. The study also aimed to propose and evaluate an algorithm based on the audiometric findings to discriminate between affected and unaffected family members before genetic linkage analysis.

Study design: The study design was a retrospective analysis of the audiometric data of genetically affected and unaffected patients.

Setting: The study was conducted at a tertiary referral center.

Patients: A total of 17 genetically affected and 54 unaffected family members were studied.

Interventions: Pure-tone audiometry with air and bone conduction and construction and evaluation of an algorithm were performed.

Main outcome measures: The type and degree of hearing loss as compared to age and gender-dependent values according to the International Organization for Standardization 7029 standard were measured. For this comparison, the variable "hearing standard deviations" (HSD) is introduced and is defined as the number of standard deviations that a hearing threshold is lying above the age and gender-related median at the given frequency. A description of the algorithm and an evaluation in terms of alpha- and beta-error also were measured.

Results: The hearing loss is nonsyndromic, sensorineural, moderate-to-moderately severe (pure-tone average, 51 dB at age 18 years), with an early onset (probably prelingual) and no progression. It affects all frequencies but mainly the midfrequencies (500, 1,000, and 2,000 Hz). The algorithm consists of an analysis of variance to determine the frequency that is most sensitive for the genetic trait under study and on the ranking of the family members according to their hearing loss (HSD) at this frequency. Individual persons are labeled as "affected" or "unaffected" according to this ranking.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Audiometry, Pure-Tone
  • Bias
  • Child
  • Chromosome Aberrations / genetics*
  • Chromosome Disorders
  • Chromosome Mapping
  • Chromosomes, Human, Pair 11*
  • Discriminant Analysis
  • Female
  • Genes, Dominant / genetics*
  • Hearing Loss, Sensorineural / congenital*
  • Hearing Loss, Sensorineural / diagnosis
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Reproducibility of Results
  • Retrospective Studies
  • Sensitivity and Specificity