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Otol Neurotol. 2013 Jun;34(4):650-6. doi: 10.1097/MAO.0b013e31828d6501.

Identification of a SNP in a regulatory region of GJB2 associated with idiopathic nonsyndromic autosomal recessive hearing loss in a multicenter study.

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  • 1Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria.

Abstract

HYPOTHESIS:

Additional genetic changes in the regulatory region of the human GJB2 gene encoding the gap junction protein (Connexin 26) may contribute to sensorineural hearing loss.

BACKGROUND:

Mutations in GJB2 cause up to 50% of autosomal recessive nonsyndromic hearing impairment (NSHI).

METHODS:

In the present study, we screened the putative 5' GJB2 regulatory region for novel alterations.

RESULTS:

In idiopathic familial cases of NSHI lacking known pathogenic alterations in GJB2, we identified a T→C transition (refSNP: rs117685390) in a putative transcription factor binding sequence 228 bp proximal to the transcriptional start site at a homozygous frequency of 0.125 (n = 40), significantly overrepresented in comparison to the homozygous allele frequencies of 0.043 in the normal-hearing Caucasian population (n = 211; p < 0.001). In a NSHI family, inheritance of the rs117685390 C allele segregated on independent chromosomes with NSHI in conjunction with heterozygous inheritance of c.35delG, the most common Caucasian mutation in the GJB2 coding region. In a patient group (n = 32) bearing heterozygous pathogenic c.35delG mutations, - rs117685390 C allele homozygosity was also highly overrepresented (0.25; p < 0.001) and not exclusively linked to the c.35delG mutation in cis in patients homozygous for c.35delG. However, in the majority of NSHI homozygous c.35delG chromosomes examined (91/94), c.35delG homozygosity was linked to the rs117685390 C allele in cis.

CONCLUSION:

These results suggest that the rs117685390 C allele could represent a biomarker for the development of NSHI in Caucasian populations and may be included in risk assessment for the development of NSHI.

PMID:
23640091
[PubMed - indexed for MEDLINE]
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