Kytövuori Laura, Kärppä Mikko, Tuominen Hannu, Uusimaa Johanna, Saari Markku, Hinttala Reetta, Majamaa Kari
Research Unit of Clinical Neuroscience, University of Oulu, P.O. Box 5000, FI-90014, Oulu, Finland.
Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.
BMC Neurol. 2017 May 18;17(1):96. doi: 10.1186/s12883-017-0883-5.
Mitochondrial cytochrome c oxidase 2, MT-CO2, encodes one of the three subunits, which form the catalytic core of cytochrome c oxidase (COX), complex IV. Mutations in MT-CO2 are rare and the associated phenotypes are variable including nonsyndromic and syndromic forms of mitochondrial diseases.
We describe a 30-year-old man with cognitive decline, epilepsy, psychosis, exercise intolerance, sensorineural hearing impairment, retinitis pigmentosa, cataract and lactic acidosis. COX-deficient fibers and ragged red fibers were abundant in the muscle. Sequencing of mitochondrial DNA (mtDNA) revealed a novel frameshift mutation m.8156delG that was predicted to cause altered C-terminal amino acid sequence and to lead to truncation of the COX subunit 2. The deletion was heteroplasmic being present in 26% of the mtDNA in blood, 33% in buccal mucosa and 95% in muscle. Deletion heteroplasmy correlated with COX-deficiency in muscle histochemistry. The mother and the siblings of the proband did not harbor the deletion.
The clinical features and muscle histology of the proband suggested a mitochondrial disorder. The m.8156delG deletion is a new addition to the short list of pathogenic mutations in the mtDNA-encoded subunits of COX. This case illustrates the importance of mtDNA sequence analysis in patients with an evident mitochondrial disorder.
线粒体细胞色素c氧化酶2（MT - CO2）编码构成细胞色素c氧化酶（COX）催化核心的三个亚基之一，即复合体IV。MT - CO2中的突变罕见，相关表型多样，包括线粒体疾病的非综合征型和综合征型。
我们描述了一名30岁男性，有认知功能减退、癫痫、精神病、运动不耐受、感音神经性听力障碍、色素性视网膜炎、白内障和乳酸性酸中毒。肌肉中富含COX缺乏纤维和破碎红纤维。线粒体DNA（mtDNA）测序揭示了一种新的移码突变m.8156delG，预计会导致C末端氨基酸序列改变，并导致COX亚基2截短。该缺失为异质性，在血液中的mtDNA中占26%，在颊黏膜中占33%，在肌肉中占95%。缺失异质性与肌肉组织化学中的COX缺乏相关。先证者的母亲和兄弟姐妹未携带该缺失。
先证者的临床特征和肌肉组织学提示线粒体疾病。m.8156delG缺失是COX的mtDNA编码亚基致病突变短名单中的新增成员。该病例说明了mtDNA序列分析在明显线粒体疾病患者中的重要性。
