精神发育迟滞荧光原位杂交染色体亚端粒的研究

Chromosome subtelomeric analysis by FISH in patients with mental retardation

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 4 6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 >4 5 0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 To Tel Vysion TMDNA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 2 q和 6 q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

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 ToTelVysionTM DNA probes. Abnormal findings were confirmed by FISH with a specific subtelomeric probes and family studies were carried out to determine its inheritance. Results: 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.