基因确诊的43例I型亚历山大病的自然病程特点与基因型分析  

Follow-up and genetic study of 43 Chinese children with type I Alexander disease

作　　者：班婷婷[1] 吴晔[1] 张仲斌[1] 臧莉莉[1] 王静敏[1] 姜玉武[1] Ban Tingting Wu Ye Zhang Zhongbin Zang Lili Wang Jingmin Jiang Yuwu(Department of Pediatrics, Peking University First Hospital, Beijing 100034, China)

机构地区：[1]北京大学第一医院儿科,100034

出　　处：《中华儿科杂志》2017年第7期504-508,共5页Chinese Journal of Pediatrics

基　　金：国家自然科学基金（81171065）;国家科技支撑计划（2012BAI09B04）

摘　　要：目的了解Ⅰ型亚历山大病（AxD）患儿的临床表型及基因型特点。方法2005至2016年于北京大学第一医院儿科基因确诊的Ⅰ型AxD患儿共43例（男23例、女20例），回顾性病例分析Ⅰ型AxD患儿病史、体格检查资料及头颅磁共振成像（MRI）等辅助检查，并于2010年12月、2012年2月、2014年6月、2016年1月进行4次集中临床随访，对患儿的临床表型及基因型特点进行总结。结果43例Ⅰ型AxD患儿末次随访年龄中位数为11.71（10.27，13.15）岁。典型临床表现为发育迟滞（79%，34例），癫痫发作（86%，37例），头围大（中位数头围为正常第90百分位）及发作性加重（27%，13例）等。长期随访发现7岁后患儿运动功能出现明显倒退，末次随访时患儿社会生活能力评分中位数为8（6，10）分（轻度落后）。在基因确诊的Ⅰ型AxD患儿中共发现17种不同的突变，41例（95%）患儿为新生突变。发现Ⅰ型AxD患儿的3个热点突变：p.Arg239（35%，15/34），p.Arg79（26%，11/43）及p.Arg88（16%，7/43）。结论Ⅰ型AxD的临床特点为发育迟滞、反复癫痫发作、头围大及发作性加重，少数患儿出现脑干症状、精神异常、脊柱侧弯或后凸等；Ⅰ型AxD患儿7岁后运动功能出现明显倒退。Objective To identify the clinical and genetic characteristics in 43 Chinese children diagnosed with type I Alexander disease （AxD）. Method Forty-three type I AxD cases identified by glial fibrillary acidic protein （GFAP） gene mutations in Peking University First Hospital from 2005 to 2016 were followed up. The data of medical history, physical examination and magnetic resonance imaging （MRI） were collected. All these patients were followed up in December 2010, Febury 2012, June 2014 and January 2016, respectively. Result Forty-three patients were genetically confirmed as type I AxD and the median age at the last visit was 11.71 years （ 10. 27, 13. 15）. The characteristic clinical manifestations of these type I AxD patients were developmental delay （79%, 34/43） , seizures （86%, 37/43）, macrocephaly （the median percentile of head circumference is 90% ） , and paroxysmal deterioration （27% , 13/43）. All the 43 patients＇ brain MRI satisfied typical MRI features proposed by van der Knaap. According to the analysis of the long-term follow-up, patients with type I AxD began to have obvious regression in motor function after 7 years of age, and the social life ability was milally impaired 8 （6,10）scores at the last tollow-up. Seventeen heterozygous missense mutations of GFAP were identified in 43 genetically confirmed patients, and 4 mutations were novel. The mutations in 41 patients （95%, 41/43） were de novo. Three hot spots of mutation in Chinese patients were found ： p. Arg239 （ 35%, 15/34 ）, p. Arg79 （ 26%, 11/43 ） and p. R88 （16% ,7/43 ）. Conclusion The characteristic clinical manifestations of type I AxD patients are developmental delay, seizures, macrocephaly and paroxysmal deterioration. Moreover, a few patients may present with brain stem symptoms, mental abnormalities, scoliosis or kyphosis. Patients with type I AxD may show significant regression in motor function after 7 years of age.

关 键 词：Alexander病 神经胶质原纤维酸性蛋白质 基因 随访研究 

分 类 号：R748[医药卫生—神经病学与精神病学]