Tiranti V, Hoertnagel K, Carrozzo R, Galimberti C, Munaro M, Granatiero M, Zelante L, Gasparini P, Marzella R, Rocchi M, Bayona-Bafaluy M P, Enriquez J A, Uziel G, Bertini E, Dionisi-Vici C, Franco B, Meitinger T, Zeviani M
Istituto Nazionale Neurologico, Divisione di Biochimica e Genetica, 20133 Milano, Italy.
Am J Hum Genet. 1998 Dec;63(6):1609-21. doi: 10.1086/302150.
Leigh disease associated with cytochrome c oxidase deficiency (LD[COX-]) is one of the most common disorders of the mitochondrial respiratory chain, in infancy and childhood. No mutations in any of the genes encoding the COX-protein subunits have been identified in LD(COX-) patients. Using complementation assays based on the fusion of LD(COX-) cell lines with several rodent/human rho0 hybrids, we demonstrated that the COX phenotype was rescued by the presence of a normal human chromosome 9. Linkage analysis restricted the disease locus to the subtelomeric region of chromosome 9q, within the 7-cM interval between markers D9S1847 and D9S1826. Candidate genes within this region include SURF-1, the yeast homologue (SHY-1) of which encodes a mitochondrial protein necessary for the maintenance of COX activity and respiration. Sequence analysis of SURF-1 revealed mutations in numerous DNA samples from LD(COX-) patients, indicating that this gene is responsible for the major complementation group in this important mitochondrial disorder.
与细胞色素c氧化酶缺乏相关的 Leigh 病（LD[COX-]）是婴幼儿期最常见的线粒体呼吸链疾病之一。在 LD(COX-) 患者中，尚未发现编码COX蛋白亚基的任何基因发生突变。利用基于 LD(COX-) 细胞系与几种啮齿动物/人类rho0杂种融合的互补分析，我们证明正常人类9号染色体的存在可挽救COX表型。连锁分析将疾病基因座限制在9号染色体q臂的亚端粒区域，在标记 D9S1847 和 D9S1826 之间的7厘摩区间内。该区域内的候选基因包括SURF-1，其酵母同源物（SHY-1）编码维持COX活性和呼吸所必需的线粒体蛋白。对SURF-1的序列分析揭示了来自LD(COX-)患者的大量DNA样本中的突变，表明该基因是这种重要线粒体疾病中主要互补组的病因。
