Introduction: Mutations in GJB2 are the most common cause of non-syndromic autosomal recessive hearing impairment, ranging from mild to profound. Mutation analysis of this gene is widely available as a genetic diagnostic test.
Objective: To assess a possible genotype-phenotype correlation for GJB2.
Design: Retrospective analysis of audiometric data from people with hearing impairment, segregating two GJB2 mutations.
Subjects: Two hundred and seventy seven unrelated patients with hearing impairment who were seen at the ENT departments of local and university hospitals from Italy, Belgium, Spain, and the United States, and who harboured bi-allelic GJB2 mutations.
Results: We found that 35delG homozygotes have significantly more hearing impairment, compared with 35delG/non-35delG compound heterozygotes. People with two non-35delG mutations have even less hearing impairment. We observed a similar gradient of hearing impairment when we categorised mutations as inactivating (that is, stop mutations or frame shifts) or non-inactivating (that is, missense mutations). We demonstrated that certain mutation combinations (including the combination of 35delG with the missense mutations L90P, V37I, or the splice-site mutation IVS1+1G>A, and the V37I/V37I genotype) are associated with significantly less hearing impairment compared with 35delG homozygous genotypes.
Conclusions: This study is the first large systematic analysis indicating that the GJB2 genotype has a major impact on the degree of hearing impairment, and identifying mild genotypes. Furthermore, this study shows that it will be possible to refine this correlation and extend it to additional genotypes. These data will be useful in evaluating habilitation options for people with GJB2 related deafness.
- ASPCR, allele-specific polymerase chain reaction
- HL, hearing loss
- ISO, International Standards Organization
- PTA, pure tone average
- SSCP, single strand conformational polymorphism
Statistics from Altmetric.com
↵* All authors contributed equally
This research was performed within the framework of the Interuniversity Attraction Poles program P5/19 of the Federal Office for Scientific, Technical, and Cultural Affairs, Belgium. This study was supported by grant G.0277.01 from the FWO (G Van Camp), NIH grant RO1-DC02842 (R J H Smith), and grants from the European Community (QLG2-CT-1999-00988), CAICYT of Spanish Ministerio de Ciencia y Tecnología (SAF99-0025), and the Spanish Fondo de Investigaciones Sanitarias (FIS 00/0244) (F Moreno and I del Castillo).
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.