GM1神经节苷脂累积病6例患儿临床及遗传学研究  

Clinical and molecular genetic analysis of six patients with GM1 gangliosidosis

作　　者：冀浩然 肖江喜[2] 李东晓[1] 李改梅[3] 吴晔[1] 延会芳 杨艳玲[1] 张月华[1] 姜玉武[1] 王静敏[1] Ji Haoran Xiao Jiangxi Li Dongxiao Li Gaimei Wu Ye Yah Huifang Yang Yanling Zhang Yuehua Jiang Yuwu Wang Jingmin(Department of Pediatrics, Peking University First Hospital, Beijing 100034, China Department of Radiology,Peking University First Hospital , Beijing 1000 34 , Chin Department of Neurology, First Hospital of Shanxi Medical University, Taiynan 030001, China)

机构地区：[1]北京大学第一医院儿科,100034 [2]北京大学第一医院影像科,100034 [3]山西医科大学第一医院神经内科,太原030001

出　　处：《中华实用儿科临床杂志》2016年第20期1536-1540,共5页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家重点基础研究发展计划（2012CB944602）;“十二五”国家科技支撑计划（2012BA109804）;国家自然科学基金（30973227）;儿科遗传性疾病分子诊断与研究北京市重点实验室项目（BZ0317）

摘　　要：目的分析6例GM1神经节苷脂累积病患儿临床及遗传学特点。方法收集2014年4月至2015年8月在北京大学第一医院儿科就诊的6例GM1神经节苷脂累积病先证者及其家系成员临床资料，并进行白细胞溶酶体酶活性检测，分析临床特点；进行β-半乳糖苷酶-1（GLB1）基因突变检测，分析遗传学特点。结果1．临床特点：6例患儿均于出生8个月内起病。患儿均有智力运动发育迟缓伴倒退，多数患儿有惊跳反应、癫痫史、肌张力低下，少数患儿有视听力损害、Mongolian斑、肝大及体格生长落后。头颅磁共振成像（MRI）均表现髓鞘形成不良，4例见他像丘脑低信号，4例见大脑和／或小脑萎缩。患儿溶酶体酶活性检测均示酸性GLB活性降低。6例患儿均符合GM1神经节苷脂累积病诊断，其中Ⅰ型3例，Ⅱ型3例。2．遗传学特点：6例患儿共发现10种GLBl突变：0．520T〉C（P．Y174H）、c．622C〉T（P．R208C）、c．550C〉T（P．Q184x）、C．446C〉T（P．S149F）、c．266A〉G（P．H89R）、c．601C〉T（P．B201C）、0．148T〉A（P．Y50N）、c．618delC（P．R208MsX21）、c．1343A〉T（P．D448V）、c．410C〉A（P．A137D），其中c．550C〉T（P．Q184X）、c．148T〉A（P．Y50N）、c．618delC（P．R208MsX21）、0．266A〉G（P．H89R）及c．410C〉A（P．A137D）为未报道新突变。4例患儿为复合杂合突变，2例为纯合突变，均分别遗传自表型正常的父母。结论本研究确诊6例GM1神经节苷脂累积病患儿，发现5种GLB1未报道新突变，扩大了GLB1突变谱，为患儿家庭提供准确的遗传咨询及产前诊断。Objective To analyze the clinical and molecular genetic features in 6 pedigrees with GM1 ganglio- sidosis. Methods Clinical data of 6 patients with GM1 gangliosidosis were collected from April 2014 to August 2015 in Department of Pediatrics, Peking University First Hospital. Lysosomal enzyme assays for examining its activity in white blood cell were used to analyze clinical characteristics. Lysosomal enzyme assays were used to examine the mutation of β - galactosidase - 1 （ GLB1 ）. Polymerase chain reaction （PCR） and Sanger sequencing were used to detect GLB1 mu- tations to analyze the genetic characteristics. Results （ 1 ） Clinical characteristics ： all 6 patients showed their initial symptoms before 8 months old. Developmental retardation and regression were seen in all patients. Startle response, epi- lepsy, hypotonia were found in most patients, and hearing and visual loss, Mongolian spots, hepatomegaly and growth de- lay were found as well. Hypomyelination was found in all 6 patients＇ cranial MRI. Four cases of T2WI hyperintensity in thalami and 4 cases of cerebral and/or cerebellar atrophy were seen as well. Activity of GLB in all 6 patients decreased. Three patients were diagnosed with GM1 gangliosidosis type Ⅰ while 3 patients were GM1 gangliosidosis type Ⅱ. （2） Ge- netic characteristics ： 10 GLB1 mutations of c. 520T 〉 C （p. Y174H）, c. 622C 〉 T （p. R208C）, c. 550C 〉 T （p. Q184X）, c. 446C 〉 T （ p. S149F）, c. 266 A 〉 G （ p. H89R）, c. 601C 〉 T （ p. R201C ）, c. 148T 〉 A （ p. YSON）, c. 618delC （p. R208MsX21 ）, c. 1343A 〉 T（p. IM48V）, c. 410C 〉 A（p. A137D） were detected in total,including 5 novel mutations： c. 550C 〉T（p. Q184X） ,c. 148T 〉 A（p. YSON） ,c. 618delC （p. R208MsX21 ） ,c. 266T 〉 C（p. H89R） and c. 410C 〉 A （p. A137D） ;GLB1 mutations in 4 patients were compound heterozygous while the other 2 were homozygous, and all were inherited from their healthy parents. Conclusions Six patients were di

关 键 词：GM1神经节苷脂累积病 Β-半乳糖苷酶 突变 

分 类 号：R725.8[医药卫生—儿科]