Department of Otolaryngology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Itabashi, Tokyo, Japan.
J Hum Genet. 2010 Mar;55(3):147-54. doi: 10.1038/jhg.2009.143. Epub 2010 Jan 29.
Sensorineural hearing loss (HL) is one of the most frequent clinical features in patients with mitochondrial diseases caused by mitochondrial DNA (mtDNA) mutations, and hearing is impaired in over half of all cases with mitochondrial disorders. This study analyzed 373 patients with suspected hereditary HL using an extensive and rapid suspension-array screening system for 29 major mtDNA mutations, including the m.1555A>G homoplasmic mutation in the MT-RNR1 gene, which causes non-syndromic sensorineural HL and aminoglycoside-induced HL, and the m.3243A>G heteroplasmic mutation in the MT-TL1 gene. This method is rapid and suitable for large-scale screening because universal 96-well plates are available for use, and because an analysis of each plate can be completed within 1 h. This system detected five different mtDNA mutations in 24 of the 373 (6.4%) patients. The m.1555A>G and m.3243A>G mutations were detected in 11 (2.9%) and 9 (2.7%) patients, respectively. In addition, three mutations, that is, m.8348A>G in the MT-TK gene, m.11778G>A in the MT-ND4 gene and 15498G>A in the MT-CYB gene were detected in one patient for each. This screening system is useful for the genetic diagnosis and epidemiological study of both syndromic and non-syndromic HL.
感音神经性听力损失（HL）是由线粒体 DNA（mtDNA）突变引起的线粒体疾病患者最常见的临床特征之一，超过一半的线粒体疾病患者存在听力受损。本研究使用广泛且快速的悬浮阵列筛查系统对 373 名疑似遗传性 HL 患者进行了分析，该系统针对 29 种主要 mtDNA 突变进行了筛查，包括 MT-RNR1 基因中的 m.1555A>G 同质性突变，该突变可导致非综合征性感音神经性 HL 和氨基糖苷类诱导性 HL，以及 MT-TL1 基因中的 m.3243A>G 异质性突变。这种方法快速且适合大规模筛查，因为可以使用通用的 96 孔板，并且可以在 1 小时内完成对每个板的分析。该系统在 373 名患者中的 24 名（6.4%）中检测到五种不同的 mtDNA 突变。m.1555A>G 和 m.3243A>G 突变分别在 11 名（2.9%）和 9 名（2.7%）患者中检测到。此外，在一名患者中分别检测到 MT-TK 基因中的 m.8348A>G、MT-ND4 基因中的 m.11778G>A 和 MT-CYB 基因中的 15498G>A 这三种突变。该筛查系统对于综合征性和非综合征性 HL 的遗传诊断和流行病学研究均具有重要意义。
