精神发育迟滞荧光原位杂交染色体亚端粒的研究

目的:探讨染色体亚端粒重排在特发性精神发育迟滞(mental retardation MR)的病因学意义及发生率.方法:对46例诊断不明的MR患儿进行荧光原位杂交(fluorescence in situ hybridization FISH) 染色体亚端粒分析.研究对象入选标准:①MR伴以下条件2项或以上:头面部异常特征,手足、生殖器或内脏器官先天异常发现,宫内生长发育迟缓史,生后异常生长发育,阳性家族史;②>450显带分辨水平染色体分析结果正常;③排除临床可识别的遗传或环境致病因素.选用ToTelVysionTM DNA探针进行染色体亚端粒FISH分析,发现缺失或易位者,需由另一亚端粒特异性探针证实诊断,并用同一探针对父母样本进行FISH分析.结果:检测到2q和6q末端微小缺失各1例,本组样本中-重度MR亚端粒缺失的发生率为7.6%(1/13),轻度MR的发生率为3.0%(1/33),其中1例亚端粒微小缺失遗传自其有相同改变的父亲.结论:研究结果支持染色体亚端粒异常为MR的重要病因,FISH分析为发现隐藏亚端粒缺失的有力工具.建议对临床怀疑有染色体异常的MR,在常规分析的基础上进一步作亚端粒FISH分析.

Chromosome subtelomeric analysis by FISH in patients with mental retardation

OBJECTIVE: To assess subtelomeric chromosome anomalies in patients with idiopathic mental retardation (MR). METHODS: Subtelomeric screening was performed in 46 patients with undiagnosed mental retardation. The patients were selected based on the following criteria: (1) MR with two or more of the following conditions: dysmorphic features, prenatal growth retardation, postnatal growth abnormalities, a suggestive family history; (2) chromosome karyotype at the level >450 bands being normal; (3) exclusion of other identified genetic or environmental diagnosis. Fluorescence in situ hybridization (FISH) was performed using ToTelVysion DNA probes. Abnormal findings were confirmed by FISH with a specific subtelomeric probes and family studies were carried out to determine its inheritance. RESULT: Clinically significant aberrations were detected in two cases with 6q and 2q terminal microdeletion. The deletion in one case was inherited from a similarly affected father. Subtle chromosomal subtelomeric abnormalities occurred with a frequency of 7.6% in children with moderate to severe mental retardation and of 3.0% in the children with mild retardation. CONCLUSION: The results suggest that cryptic abnormalities of the ends of chromosomes might represent a significant cause of mental retardation, and screening for subtelomeric rearrangements might be warranted in children with unexplained mental retardation.