Phenotype/genotype correlations in a DFNB1 cohort with ethnical diversity

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27 Scopus citations


Objectives/Hypothesis: The aim of this study was to 1) determine the prevalence of DFNB1 in a cohort of children with prelingual nonsyndromic sensorineural hearing loss (HL), 2) study phenotype/genotype correlations, and 3) establish guidelines for genetic counseling of DFNB1. Study Design: Prospective cohort study. Methods: A total of 119 unrelated children (107 sporadic and 12 familial cases) with prelingual nonsyndromic HL underwent mutational screening for DFNB1 in the noncoding and coding exons of GJB2, in addition to the del(GJB6-D13S1830) mutation of GJB6. Information regarding demographics, HL, developmental milestones, inner ear high resolution computed tomography, hearing habilitation, and associated phenotypic manifestations were collected in probands with biallelic pathogenic mutations. Results: The prevalence of DFNB1 in cases of prelingual nonsyndromic HL was 26% (25% in sporadic and 50% in familial cases). In regards to ethnicity, 19 probands were white and 12 probands of Hispanic ancestry had a mixed racial origin (black, Native-American, white). Greater allelic heterogeneity was shown with Hispanics of mixed descent exhibiting 10 of 12 GJB2 allelic variants, whereas whites had 4 of 10 allelic variants (Fisher exact test, P =.033); both ethnic groups had the GJB6 deletion. The frequency of deaf carriers of the most commonly found mutation (c.35delG) was 8% and higher than that of expected for the general population (Fisher exact test, P =.015). The hearing phenotype was variable in terms of degree of impairment (from mild to profound), onset, symmetry and progression, and there was no correlation with any specific genotype class. DFNB1 probandshad normal gross motor development, and the frequency of computed tomography abnormalities of the inner ear was low at 8%. No other specific associated phenotypic manifestations were identified. Conclusions: DFNB1 is the most common identifiable etiology of nonsyndromic prelingual deafness both in sporadic and familial cases in this cohort with ethnic diversity. The greater allelic variability observed in Hispanics and the high frequency of deaf probands carrying a single allelic variant of DFNB1 support extending the screening to noncoding regions of GJB2 and to the remaining DFNB1 locus. Most probands have a congenital HL that is stable, symmetrical and without associated manifestations, but the audiometric profile should not be the only criteria for offering mutational screening of DFNB1 because of the observed variability. These data can be applied to direct the clinical evaluation and effectively counsel families of children with DFNB1.

Original languageEnglish (US)
Pages (from-to)2014-2023
Number of pages10
Issue number11
StatePublished - Nov 2008


  • Cochlear implant
  • Computed tomography
  • Congenital HL
  • Connexin 26
  • Connexin 30
  • DFNB1
  • Genetic counseling
  • Genetic testing
  • GJB2
  • GJB6
  • Hispanics
  • HL
  • Motor development
  • Nonsyndromic recessive HL
  • Prevalence

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Medicine(all)


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