Konings Annelies, Van Camp Guy, Goethals Alain, Van Eyken Els, Vandevelde Ann, Ben Azza Jamila, Peeters Nils, Wuyts Wim, Smeets Hubert, Van Laer Lut
Department of Medical Genetics, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, Antwerp, Belgium.
Mitochondrion. 2008 Dec;8(5-6):377-82. doi: 10.1016/j.mito.2008.08.001. Epub 2008 Aug 26.
Specific mitochondrial DNA (mtDNA) mutations in 12SrRNA and tRNASer(UCN) cause non-syndromic hearing loss (NSHL). In this study, we screened 466 hearing loss (HL) patients, negative for GJB2 mutations, for mutations in the two mtDNA genes and flanking regions. In total, 43 different variants were identified, 31 of which were polymorphisms, one was a mutation (m.1555A-->G), two were known variants of controversial pathological nature (m.827A-->G and m.961delTinsC(n)) and nine were newly identified variants. The frequency of m.1555A-->G in this set of HL patients was 0.3%, which was lower than expected. To assess the putative causative nature of controversial or newly identified variants, the frequencies of these variants were determined in 400 Belgian control subjects, and their effect on the secondary structure and their conservation among different species was determined. Our data provide further support for a polymorphic nature of the controversial m.961delTinsC(n) variant. In addition, two of the newly identified variants, m.636A-->G in the 12SrRNA flanking tRNA(Phe) and m.990T-->C in 12SrRNA, may be new candidates for pathogenic HL variants. If the pathogenic nature of m.636A-->G can be confirmed, this would be the first NSHL mutation in tRNA(Phe).
12SrRNA和tRNASer(UCN)中的特定线粒体DNA (mtDNA) 突变会导致非综合征性听力损失 (NSHL)。在本研究中，我们对466名GJB2突变阴性的听力损失 (HL) 患者进行了这两个mtDNA基因及其侧翼区域的突变筛查。总共鉴定出43种不同的变异，其中31种是多态性，1种是突变 (m.1555A→G)，2种是具有争议性病理性质的已知变异 (m.827A→G和m.961delTinsC(n))，9种是新鉴定的变异。在这组HL患者中，m.1555A→G的频率为0.3%，低于预期。为了评估有争议的或新鉴定的变异的假定致病性质，在400名比利时对照受试者中确定了这些变异的频率，并确定了它们对二级结构的影响以及在不同物种中的保守性。我们的数据为有争议的m.961delTinsC(n) 变异的多态性性质提供了进一步支持。此外，新鉴定的两个变异，位于tRNA(Phe) 侧翼的12SrRNA中的m.636A→G和12SrRNA中的m.990T→C，可能是致病性HL变异的新候选者。如果m.636A→G的致病性质能够得到证实，这将是tRNA(Phe) 中的首个NSHL突变。
