中国儿童孤独症SHANK3拷贝数变异及其临床表型特征  

Copy-number variations of SHANK3 and related clinical phenotypes in children with autism

作　　者：陈碧媛[1] 邹小兵[1] 章钧[2] 邓红珠[1] 李建英[1] 李丽英[3] 唐春[1] 邹园园[1] 

机构地区：[1]中山大学附属第三医院儿童发育行为中心,广州510630 [2]中山大学附属第三医院产科实验室,广州510630 [3]中山大学北校区医学部办公室,广州

出　　处：《中华儿科杂志》2011年第8期607-611,共5页Chinese Journal of Pediatrics

基　　金：基金项目：中山大学2009年度个别青年人才资助计划（A01291）

摘　　要：目的检测典型孤独症患儿SHANK3基因拷贝数变异（CNVs）发生率并描述其临床表型特征，并探讨临床应用多重连接依赖探针扩增技术（MLPA）进行孤独症病因学诊断的可行性。方法收集本院确诊为典型孤独症的患儿及其直系亲属的基因组DNA，采用MRCP343-C1AUTISM-1MLPA试剂盒进行CNVs筛查。结果共收集来自102个家系的109例典型孤独症患儿，男女比例为4．45：1。发现2例患儿出现SHANK3微缺失，检出率约为2％（2／109）。结论SHANK3基因的CNVs可能解释约2％的典型孤独症病例，是孤独症的一个重要遗传学变异基础；阳性病例倾向于出现严重的三大核心症状及智力缺损的表型；MLPA作为快速、准确的CNVs检测方法，有助于临床开展孤独症的病因学研究。Objective To explore possible relationship between copy-number variations （CNVs） in 15q11-13,16p11 and SHANK3 gene by using multiplex ligation-dependent probe amplification （MLPA） and the phenotypes in children with autism and to further explore the clinical application of MLPA to make an etiological diagnosis of Autism. Methods The diagnosed of autism was made according to the criteria of the ICD-10 and DSM-Ⅳ, with typical cluster of symptoms comprise social disability, communication impairments and repetitious behaviors. MLPA KIT P343-C1 AUTISM-1 was used to detect and describe the incidence of CNVs in these three domains. Results Among 109 cases collected from 102 autistic pedigrees, 2 individuals had SHANKA microdeletion, accounting for approximately 2% （2/109） of cases, suggesting the proportion of SHANK3 microdeletion might contribute to typical autism. The phenotypic traits of patients with SHANK3 microdeletions showed homogenicity in severe core symptoms and mental retardation. Conclusions SHANK3 microdeletion is an important genetics component for autism, which may explain 2% typical autism cases. SHANKA microdeletion might explain autistic core symptoms and mental retardation. MLPA is a sensitive and a high throughput technique to detect CNVs in specific DNA segments, which is beneficial for further investigation of etiology of autism.

关 键 词：孤独症 核酸扩增技术 变异(遗传学) 

分 类 号：R749.94[医药卫生—神经病学与精神病学]