核黄素反应性脂质沉积性肌病20个家系的电子转移黄素蛋白脱氢酶基因存在热点突变  

Hot spot mutations in electron transfer flavoprotein dehydrogenase gene of riboflavin responsive lipid storage myopathy in 20 Chinese families

作　　者：王韵[1] 赵丹华[1] 洪道俊[1] 王朝霞[1] 袁云[1] 

机构地区：[1]北京大学第一医院神经内科,100034

出　　处：《中华神经科杂志》2011年第5期309-313,共5页Chinese Journal of Neurology

摘　　要：目的报道20个核黄素反应性脂质沉积性肌病（RR-LSM）患者的电子转移黄素蛋白脱氢酶（ETFDH）基因检查结果。方法对2003年1月至2010年5月我院神经科收治的24例RR—LSM患者（来自20个我国大陆北方地区RR—LSM家系，其中16个家系各有1例患者，其余4个家系各有2例发病者）的临床特点进行分析。对24例患者、11名无症状家系成员以及100名健康人行ETFDH基因检查。结果24例患者发病年龄为（27．9±9．9）岁，主要症状为四肢无力（21例，87．5％）、咀嚼困难（15例，62．5％）、颈肌无力（14例，58．3％）和肌痛（14例，58．3％）等。18例患者的血代谢筛查均提示脂酰肉碱升高，17例患者中有15例存在戊二酸尿症。我们发现19个家系存在17种ETFDH基因点突变，包括13种错义突变、2种剪切突变和2种无义突变。其中患者的C．998A〉G、c．1450T〉C、c．1703T〉C、c．1717C〉T、c．821G〉A、12．643G〉A、c．251C〉T、c．1763A〉T、c．IVS7＋2T〉C、c．IVS6＋1G〉A没有出现在100名健康人中。有9个家系存在c．770A〉G（p．Y257C）突变；5个家系存在c．1227A〉C（p．IA09F）突变。结论诸多ETFDH基因新突变提示国人RR-LSM可能存在特殊的基因突变谱，其中p．Y257C与p．L409F突变可能为我国大陆北方地区的热点突变。Objective To report the spectrum of electron transfer flavoprotein dehydrogenase （ETFDH） gene mutations in 20 Chinese RR-LSM families. Methods Twenty-four RR-LSM patients in the First Hospital of Peking University from January 2003 to May 2010 were collected and the clinical characteristics were analyzed. These patients came from 20 families in North China's Mainland. Sixteen families had 1 patient each, and the other 4 families had 2 patients. ETFDH gene analysis was performed in all patients, 11 family members and 100 healthy controls. Results The mean onset age was （27.9 ±9. 9） years. The main symptoms were limb weakness （21,87.5%） , dysmasesia （ 15, 62. 5% ） , neck weakness （ 14, 58. 3% ） and myalgia （ 14, 58.3% ）. Eighteen patients had high level of acylearnitine. Fifteen of 17 patients had glutarie aciduria. Seventeen ETFDH mutations, including 13 missense mutations, 2 splice mutations, and 2 nonsense mutations, were identified in 19 families： c. 998A 〉 G, c. 1450T 〉 C, c. 1703T〉C, c. 1717C〉T, c. 821G〉A, c. 643G〉A, c. 251C 〉T, c. 1763A〉T, c. IVS7 ＋2T〉C and c. IVS6 ＋ 1G 〉 A were novel mutations which were not found in 100 healthy controls. Nine families had the mutation of c. 770A 〉 G （ p. Y257C ） and 5 families had the mutation of c. 1227A 〉 C （ p. IA09F ）. Conclusions The numerous novel mutations in ETFDH gene indicate that Chinese RR-LSM might have special mutation pattern, c. 770A 〉 G （p. Y257C） and c. 1227A 〉 C （p. L409F） may be hot spot mutations in North China's Mainland.

关 键 词：脂质贮积病 肌疾病 多种酰基辅酶A脱氢酶缺乏 电子转移黄素蛋白质类 突变 

分 类 号：R746[医药卫生—神经病学与精神病学]