title: MRPS18CP2 alleles and DEFA3 absence as putative chromosome 8p23.1 modifiers of hearing loss due to mtDNA mutation A1555G in the 12S rRNA gene.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Genes and Disease Program, Centre for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. ester.ballana@gmail.com
authors.forename: Ester
authors.initials: E
authors.lastname: Ballana
authors.forename: Josep Maria
authors.initials: JM
authors.lastname: Mercader
authors.forename: Nathan
authors.initials: N
authors.lastname: Fischel-Ghodsian
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
mesh_terms: D000483:Alleles; D002874:Chromosome Mapping; D002898:Chromosomes, Human, Pair 8; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D005810:Multigene Family; D009154:Mutation; D011544:Pseudogenes; D012335:RNA, Ribosomal / Q000235:genetics*; D013030:Spain; D023084:alpha-Defensins / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D023084:alpha-Defensins