Homozygous M34T mutation of the GJB2 gene associates with an autosomal recessive nonsyndromic sensorineural hearing impairment in Finnish families.
CONCLUSIONS
The genetic and audiological data support the hypothesis that the p.M34T is a pathogenic mutation in the Finnish population. The p.M34T mutation displays an autosomal recessive pattern of inheritance and is associated with mild to moderate nonsyndromic sensorineural hearing impairment (SNHI) in the homozygous state. The audiograms often display a hearing impairment notch at 2-4 kHz in young patients, which may aid in the early diagnosis.


OBJECTIVE
The aim of the study was to assess whether the p.M34T mutation in the GJB2 gene may associate with nonsyndromic SNHI.


METHODS
We systematically reviewed the families with children diagnosed with nonsyndromic SNHI caused by a homozygous p.M34T mutation at the Kuopio and Oulu University Hospital Clinics. The children were re-examined and audiological and genetic data were obtained from their parents and healthy siblings to study genotype-phenotype correlation.


RESULTS
We describe 11 patients from 6 families including 5 sibling pairs from 6 to 23 years of age with homozygous p.M34T genotype all having mild nonsyndromic SNHI. In addition, we found three patients with compound p.M34T mutation also exhibiting mild to moderate SNHI.
Department of Paediatrics, Child Neurology, Kuopio University Hospital, Finland.
Tuija
T
Löppönen
Aarno
A
Dietz
Marja-Leena
ML
Väisänen
Hannu
H
Valtonen
Ari
A
Kosunen
Antti
A
Hyvärinen
Jaakko
J
Ignatius
Heikki
H
Löppönen
D000293:Adolescent; D000328:Adult; D000848:Anodontia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D001299:Audiometry; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D055815:Young Adult
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; D004247:DNA