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Objective: Mitochondrial mutations have been shown to be responsible for syndromic as well as non-syndromic hearing loss. The G7444A mitochondrial DNA mutation affects COI/the precursor of tRNA(Ser(UCN)), encoding the first subunit of cytochrome oxidase. Here we report on the first Greek family with the G7444A mitochondrial DNA mutation. Methods: Clinical, cytogenetic, and molecular methods were employed in this study. Results: We describe the high variability of phenotypes among three family members harboring the G7444A mutation and also the frequent GJB2 c.35delG mutation of the nuclear genome in heterozygosity. Their phenotypes ranged from normal hearing to deafness, while the proband presented with several other symptoms. Conclusions: The G7444A mitochondrial DNA mutation has been reported in only a few cases worldwide, alone or in cosegregation with other mitochondrial DNA mutations, but to our knowledge, never before in coexistence with the GJB2 c.35delG mutation. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Mitochondrion harbors its own DNA, known as mtDNA, encoding certain essential components of the mitochondrial respiratory chain and protein synthesis apparatus. mtDNA mutations have an impact on cellular ATP production and many of them are undoubtedly a factor that contributes to sensorineural deafness, including both syndromic and non-syndromic forms. Hot spot regions for deafness mutations are the MTRNR1 gene, encoding the 12S rRNA, the MTTS1 gene, encoding the tRNA for Ser((UCN)), and the MTTL1 gene, encoding the tRNA for Leu((UUR)). We investigated the impact of mtDNA mutations in the Greek hearing impaired population, by testing a cohort of 513 patients suffering from childhood onset prelingual or postlingual, bilateral, sensorineural, syndromic or non-syndromic hearing loss of any degree for six mitochondrial variants previously associated with deafness. Screening involved the MTRNR1 961delT/insC and A1555G mutations, the MTTL1 A3243G mutation, and the MTTS1 A7445G, 7472insC and T7510C mutations. Although two patients were tested positive for the A1555G mutation, we failed to identify any subject carrying the 961delT/insC, A3243G, A7445G, 7472insC, or T7510C mutations. Our findings strongly support our previously raised conclusion that mtDNA mutations are not a major risk factor for sensorineural deafness in the Greek population.

Hearing impairment is a frequent condition, and genes have an important role in its etiology. The majority of hearing loss occurs in non-syndromic form, with deafness being the only clinically recognizable feature. More than 60 nuclear genes or loci have been shown to be involved in non-syndromic hearing loss, but mutations in mitochondrial DNA also cause hearing impairment. Mitochondrial DNA mutations usually lead to progressive hearing loss with an age of onset varying from childhood to early adulthood. It is interesting to note that there is a great variability among phenotypes between individuals harboring the same mitochondrial mutation, even within the same family, and the phenotype may range from profound deafness to completely normal hearing. In the past years, the debate on mitochondrial mutations has been about the penetrance, the tissue specificity and the mechanisms of modifier genes that can modulate the severity of the phenotypic expression of the deafness-associated mitochondrial DNA mutations. Here we summarize evidence regarding modifying genes, and we discuss the effect of the coexistence of mitochondrial and GJB2 mutations in families reported to date. Journal of Human Genetics (2010) 55, 265-269; doi:10.1038/jhg.2010.23; published online 19 March 2010

Mitochondrial DNA mutations are undoubtedly a factor that contributes to sensorineural, non-syndromic deafness. One specific mutation, the A1555G, is associated with both aminoglycoside-induced and nonsyndromic hearing impairment. The mutation is considered to be the most common of all mitochondrial DNA deafness-causing mutations but its frequency varies between different Populations. Here we report on the first large screening of the A1555G mitochondrial DNA mutation in the Greek population. The aim of this study was to determine the frequency of the A1555G mutation in Greek sensorineural, non-syndromic deafness patients, with childhood onset. We screened 478 unrelated Greek patients with hearing loss of any degree and found two individuals harboring the A1555G mutation (0.42%). Both cases had been subjected to aminoglycosides. They were prelingual, familial and homoplasmic for the A1555G mutation. One of the Cases Was also found heterozygous for the frequent GJB2 35delG mutation, while the other case was negative, The A1555G mutation seems to be less common than in other European populations. (C) 2009 Elsevier Inc. All rights reserved.