Email updates

Keep up to date with the latest news and content from BMC Medical Genetics and BioMed Central.

Open Access Research article

MRPS18CP2 alleles and DEFA3 absence as putative chromosome 8p23.1 modifiers of hearing loss due to mtDNA mutation A1555G in the 12S rRNA gene

Ester Ballana1, Josep Maria Mercader12, Nathan Fischel-Ghodsian3 and Xavier Estivill1245*

Author Affiliations

1 Genes and Disease Program, Centre for Genomic Regulation (CRG), Barcelona, Catalonia, Spain

2 CIBER en Epidemiología y Salud Pública (CIBERESP), Barcelona, Catalonia, Spain

3 Cedars-Sinai Medical Center and David Geffen School of Medicine at UCLA, Los Angeles, USA

4 CeGen, Spanish National Genotyping Centre, Barcelona, Catalonia, Spain

5 Universitat Pompeu Fabra (UPF), Barcelona, Catalonia, Spain

For all author emails, please log on.

BMC Medical Genetics 2007, 8:81  doi:10.1186/1471-2350-8-81

Published: 21 December 2007



Mitochondrial DNA (mtDNA) mutations account for at least 5% of cases of postlingual, nonsyndromic hearing impairment. Among them, mutation A1555G is frequently found associated with aminoglycoside-induced and/or nonsyndromic hearing loss in families presenting with extremely variable clinical phenotypes. Biochemical and genetic data have suggested that nuclear background is the main factor involved in modulating the phenotypic expression of mutation A1555G. However, although a major nuclear modifying locus was located on chromosome 8p23.1 and regardless intensive screening of the region, the gene involved has not been identified.


With the aim to gain insights into the factors that determine the phenotypic expression of A1555G mutation, we have analysed in detail different genetic and genomic elements on 8p23.1 region (DEFA3 gene absence, CLDN23 gene and MRPS18CP2 pseudogene) in a group of 213 A1555G carriers.


Family based association studies identified a positive association for a polymorphism on MRPS18CP2 and an overrepresentation of DEFA3 gene absence in the deaf group of A1555G carriers.


Although none of the factors analysed seem to have a major contribution to the phenotype, our findings provide further evidences of the involvement of 8p23.1 region as a modifying locus for A1555G 12S rRNA gene mutation.