Human mitochondrial transcription factor B1 as a modifier gene for hearing loss associated with the mitochondrial A1555G mutation.

摘要: Phenotypic expression of the deafness-associated homoplasmic A1555G mutation in mitochondrial 12S rRNA gene varies from profound congenital hearing loss to normal hearing. It has been shown that this variability clinical most patients is due complex inheritance multiple nuclear-encoded modifier genes. Human transcription factor B1 (TFB1M) proposed as a candidate for being such modifier, since it methylates adenine residues adjacent loop gene. Polymorphic markers within and TFB1M were genotyped 214 individuals 41 multiplex families with Spanish, Italian, Arab-Israeli origin. Multipoint non-parametric linkage analysis all combined revealed an NPL score 1.7 (P = 0.05), Lod 1.4 0.04). Linkage disequilibrium by Transmission Disequilibrium Test at D6S1577, microsatellite TFB1M, showed preferential non-transmission allele affected chi2 8.76; P 0.003. Sequence coding region testing intragenic SNPs did not reveal putative causative mutation. These data provide suggestive evidence phenotypic mutation, effect may occur through regulatory or splicing