Department of Medical Genetics, Archet 2 Hospital, Centre Hospitalier Universitaire de Nice, Nice, France.
Diabetes Care. 2011 Dec;34(12):2591-3. doi: 10.2337/dc11-1012. Epub 2011 Oct 12.
The m.3243A>G mutation in mitochondrial DNA (mtDNA) is responsible for maternally inherited diabetes and deafness (MIDD). Other mtDNA mutations are extremely rare.
We studied a patient presenting with diabetes and deafness who does not carry the m.3243A>G mutation.
We identified a deficiency of respiratory chain complex I in the patient's fibroblasts. mtDNA sequencing revealed a novel mutation that corresponds to an insertion of one or two cytosine residues in the coding region of the MT-ND6 gene (m.14535_14536insC or CC), leading to premature stop codons. This heteroplasmic mutation is unstable in the patient's somatic tissues.
We describe for the first time an unstable mutation in a mitochondrial gene coding for a complex I subunit, which is responsible for the MIDD phenotype. This mutation is likely favored by the m.14530T>C polymorphism, which is homoplasmic and leads to the formation of an 8-bp polyC tract responsible for genetic instability.
线粒体 DNA（mtDNA）中的 m.3243A>G 突变可导致母系遗传糖尿病和耳聋（MIDD）。其他 mtDNA 突变极其罕见。
我们研究了一位患有糖尿病和耳聋的患者，该患者不携带 m.3243A>G 突变。
我们发现患者的成纤维细胞中存在呼吸链复合物 I 缺陷。mtDNA 测序显示，MT-ND6 基因的编码区中存在一个或两个胞嘧啶残基的插入（m.14535_14536insC 或 CC），导致提前出现终止密码子。该异质突变在患者的体组织中不稳定。
我们首次描述了一个不稳定的线粒体基因突变，该突变可导致编码复合物 I 亚基的线粒体基因发生突变，从而导致 MIDD 表型。这种突变可能受到 m.14530T>C 多态性的影响，该多态性是同质的，导致形成负责遗传不稳定性的 8bp 多 C 区。
