| Title | SURF1 mutations in Chinese patients with Leigh syndrome: Novel mutations, mutation spectrum, and the functional consequences |
| Authors | Li, Yuanyuan Wen, Shumeng Li, Dongxiao Xie, Jie Wei, Xiujuan Li, Xiyuan Liu, Yi Fang, Hezhi Yang, Yanling Lyu, Jianxin |
| Affiliation | Minist Educ, Key Lab Lab Med, Zhejiang Prov Key Lab Med Genet, Wenzhou, Zhejiang, Peoples R China. Wenzhou Med Univ, Sch Lab Med & Life Sci, Wenzhou 325035, Zhejiang, Peoples R China. Zhengzhou Univ, Henan Prov Key Lab Childrens Genet & Metab Dis, Childrens Hosp, Zhengzhou 450000, Henan, Peoples R China. Tianjin Med Univ Gen Hosp, Dept Lab Med, Tianjin 300052, Peoples R China. Peking Univ, Dept Pediat, Hosp 1, Beijing 100034, Peoples R China. Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Affiliated Peoples Hosp, Hangzhou 310053, Zhejiang, Peoples R China. Wenzhou Med Univ, Chashan 325035, Wenzhou, Peoples R China. Yang, YL (reprint author), Peking Univ, Hosp 1, Beijing 100034, Peoples R China. |
| Keywords | SURF1 Mutation spectrum Frameshift Leigh syndrome Chinese population C-OXIDASE DEFICIENCY MITOCHONDRIAL DISEASE CHILDREN MICE LYMPHOCYTES BIOGENESIS EXPRESSION KNOCKOUT |
| Issue Date | 2018 |
| Publisher | GENE |
| Citation | GENE. 2018, 674, 15-24. |
| Abstract | SURF1 is an assembly factor of mitochondrial complex IV, and its mutations are the primary cause of Leigh syndrome in infants. To date, over 100 SURF1 mutations have been reported worldwide, but the spectrum of the SURF1 mutations in China remains unclear. Here, using next-generation sequencing targeting mitochondrial protein-coding sequences, we sequenced 178 patients suspected to have mitochondrial diseases. Fifteen SURF1 mutations were identified in 12 Leigh syndrome patients, of which three, c.465_466delAA, c.532A > T, and c.826_827ins AGCATCTGCAGTACATCG, were newly described. The percentage of SURF1 frameshift mutations (6/28, 21.4%) we detected in Chinese population is higher than other studies (21/106, 19.8%) with different populations, however, the percentage of missense mutations is lower in this study than others (4/28, 14.3% VS. 25/106, 23.6%). Since complex IV can be detected in cells carrying missense mutations (3/8) but not in cells carrying null mutations (0/4) by using cell model-based complementation assay, our results indicate that SURF1 mutations may be associated with worse clinical outcome in Chinese patients than other populations. However, studies with larger sample size are needed to verify this conclusion. Additionally, we found that the frameshift mutations resulting in protein truncation closer to the C-terminus are not associated with better disease prognosis. Lastly, we found that determining the levels of complex IV assembly using cell models or lymphocyte analysis rather than invasive muscle and skin fibroblast biopsy, may help predict disease progression in Leigh syndrome patients. |
| URI | http://hdl.handle.net/20.500.11897/516990 |
| ISSN | 0378-1119 |
| DOI | 10.1016/j.gene.2018.06.058 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 第一医院 |
