Nuclear factors: roles related to mitochondrial deafness.

Abstract Hearing loss (HL) is a common disorder with mitochondrial dysfunction as one of the major causes leading to deafness. Mitochondrial dysfunction may be caused by either mutations in nuclear genes leading to defective nuclear-encoded proteins or mutations in mitochondrial genes leading to defective mitochondrial-encoded products. The specific nuclear genes involved in HL can be classified into two categories depending on whether mitochondrial gene mutations co-exist (modifier genes) or not (deafness-causing genes). TFB1M , MTO1 , GTPBP3 , and TRMU are modifier genes. A mutation in any of these modifier genes may lead to a deafness phenotype when accompanied by the mitochondrial gene mutation. OPA1 , TIMM8A , SMAC/DIABLO , MPV17 , PDSS1 , BCS1L , SUCLA2 , C10ORF2 , COX10 , PLOG1 and RRM2B are deafness-causing genes. A mutation in any of these deafness-causing genes will directly induce variable phenotypic HL.