Faculty of Medicine of Sfax, Human Molecular Genetic Laboratory, University of Sfax, Tunisia.
Biochem Biophys Res Commun. 2013 Jan 11;430(2):585-91. doi: 10.1016/j.bbrc.2012.11.109. Epub 2012 Dec 5.
Mitochondrial diseases are a clinically heterogeneous group of disorders that arise as a result of dysfunction of the mitochondrial respiratory chain. Sensorineural hearing loss (SNHL) has been described in association to different mitochondrial multisystem syndromes, often involving the central nervous system, neuromuscular, or endocrine organs. In this study, we described a Tunisian young girl with hearing impairment, congenital visual loss and maternally inherited diabetes. No mutation was found in the mitochondrial tRNA(Leu(UUR)) and the 12S rRNA genes. However, we detected the m.7444G>A mutation in the mitochondrial COI/tRNA(Ser(UCN)) genes. This mutation eliminates the termination codon of the MT-CO1 gene and extends the COI polypeptide by three amino acids (Lys-Gln-Lys) to the C-terminal. The whole mitochondrial genome screening revealed the presence of a novel mutation m.6498C>A (L199I) in the mitochondrial DNA-encoded subunit I of the cytochrome c oxidase (COX). This "probably damaging" transversion affects a highly conserved domain and it was absent in 200 Tunisian controls. The studied patient was classified under the haplogroup H2a.
线粒体疾病是一组临床表现高度异质性的疾病，是由于线粒体呼吸链功能障碍引起的。感觉神经性听力损失（SNHL）已与不同的线粒体多系统综合征相关联，这些综合征通常涉及中枢神经系统、神经肌肉或内分泌器官。在这项研究中，我们描述了一名来自突尼斯的年轻女孩，她患有听力障碍、先天性视力丧失和母系遗传糖尿病。线粒体 tRNA(Leu(UUR)) 和 12S rRNA 基因中未发现突变。然而，我们在线粒体 COI/tRNA(Ser(UCN)) 基因中检测到 m.7444G>A 突变。该突变消除了 MT-CO1 基因的终止密码子，并在线粒体 COI 多肽的 C 末端延伸三个氨基酸（Lys-Gln-Lys）。整个线粒体基因组筛查显示，线粒体 DNA 编码的细胞色素 c 氧化酶（COX）亚单位 I 中存在一种新的突变 m.6498C>A（L199I）。这种“可能有害”的颠换影响高度保守的结构域，在 200 名突尼斯对照中不存在。所研究的患者被归类为 H2a 单倍群。
