首页 | 本学科首页   官方微博 | 高级检索  
     

不明原因智力障碍/脑发育迟缓患儿染色体亚端粒重组突变的检测
引用本文:Wu Y,Jiang YW,Wang XZ,Wang HF,Wang JM,Yang YL,Qin J,Zhong N,Wu XR. 不明原因智力障碍/脑发育迟缓患儿染色体亚端粒重组突变的检测[J]. 中华儿科杂志, 2007, 45(12): 906-911
作者姓名:Wu Y  Jiang YW  Wang XZ  Wang HF  Wang JM  Yang YL  Qin J  Zhong N  Wu XR
作者单位:1. 北京大学第一医院儿科,100034
2. 北京大学医学遗传中心
基金项目:教育部留学回国人员科研启动基金,北京大学第一医院留学回国基金 
摘    要:
目的联合应用多重连接依赖的探针扩增法和荧光原位杂交法检测染色体亚端粒重组,进行不明原因智力障碍/脑发育迟缓(mental retardation/developmental delay,MR/DD)的病因学研究。方法人选病例必须满足:①中一重度MR/DD;②无明确围产期异常病史;③无明确生后中毒、缺氧、中枢神经系统感染及头颅外伤等病史;④常规核型分析显示正常;⑤头颅影像及尿有机酸、氨基酸分析未提示典型遗传代谢性疾病或神经变性病;⑥男性患儿FMR1基因检测未提示脆性X综合征。并至少符合以下条件之一:①MR家族史阳性;②反复流产或围产期死亡家族史阳性;③体格发育异常;④面部畸形;⑤非面部畸形或发育异常。联合应用多重连接依赖的探针扩增法过筛和荧光原位杂交技术验证对患儿及父母标本进行染色体亚端粒重组检测。结果人组39例中发现4例阳性病例,重组分别为:①新发der(2)t(2;4)(pter;pter),文献未见报道;②新发8pter缺失,国外曾有报道,但临床表型不同;③新发15q11.2缺失,属中间重组,结合患儿临床表型,Angelman综合征可能性大;④新发11qter缺失,文献未见报道。结论首次报道2种新重组,其新发出现提示致病性可能性大;染色体亚端粒重组是遗传性MR/DD的重要病因,临床表型差异大,对原因不明的常规染色体检查无异常的MR/DD患者均应进行检测,联合应用多重连接依赖的探针扩增法和荧光原位杂交法是相对经济的确诊手段。

关 键 词:精神发育迟滞  染色体结构  端粒  重组  遗传  DNA探针  原位杂交  荧光

Detection of subtelomeric rearrangements in patients with idiopathic mental retardation/developmental delay
Wu Ye,Jiang Yu-wu,Wang Xiao-zhu,Wang Hui-fang,Wang Jing-min,Yang Yan-ling,Qin Jiong,Zhong Nan,Wu Xi-ru. Detection of subtelomeric rearrangements in patients with idiopathic mental retardation/developmental delay[J]. Chinese journal of pediatrics, 2007, 45(12): 906-911
Authors:Wu Ye  Jiang Yu-wu  Wang Xiao-zhu  Wang Hui-fang  Wang Jing-min  Yang Yan-ling  Qin Jiong  Zhong Nan  Wu Xi-ru
Affiliation:Department of Pediatrics, First Hospital, Peking University, Beijing 100034, China.
Abstract:
OBJECTIVE: To detect subtelomeric rearrangement in patients with idiopathic mental retardation/developmental delays (MR/DD) and to provide new methods and evidence for the etiologic diagnosis of MR/DD in China. METHODS: 1. Inclusion criteria: (1) Moderate to severe MR/DD; (2) no definite perinatal brain injury; (3) no toxication, hypoxia, infection of central nervous system and cranial trauma; (4) routine karyotyping is normal; (5) no evidence of typical inherited metabolic disorder or specific neurodegenerative disorders from cranial neuro-imaging and blood/urinary metabolic diseases screening; (6) no mutation of FMR1 gene in male patients plus one of the following criteria: (1) positive family history of MR; (2) positive family history of miscarriages and perinatal deaths; (3) abnormal growth; (4) facial and non-facial dysmorphism. 2. Multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH) were applied to detect subtelomeric rearrangements in patients and their parents. RESULTS: Four cases were identified from 39 selected cases with subtelomeric rearrangements (10%), including der (2) t (2; 4) (pter; pter), 11qter del, 8pter del, and 15p11.2 del. The first two abnormalities of chromosome subtelomeric regions have not been reported yet. All these cases had some small dysmorphologies, such as microcephaly, hypertelorism, low nasal bridge, and three of them had hypotonia. One case had recurrent seizure and abnormal behavior (laughter not associated with happiness), and another case with dysgenesis of corpus callosum and septum pellucidum. Family and perinatal histories were normal for all cases. All chromosome rearrangements were de novo which were not from the parents with normal phenotype. It indicated that all these abnormal rearrangements should be responsible for the mental retardation phenotype of these patients. The phenotype of case 4 was similar to Angelman syndrome, his deletion was actually a kind of interstitial rearrangements. It will be confirmed by DNA methylation test to determine whether the deleted allele was of maternal origin. CONCLUSIONS: The subtelomeric rearrangements were found in 10% patients with idiopathic MR. It indicated that subtelomeric rearrangements should be one of major reasons of MR/DD related to genetic factors. Two novel subtelomeric rearrangements were identified. These de novo rearrangements are probably disease related, because they are not inherited from their parents with normal phenotype. The detection should be carried out for all the patients with idiopathic MR/DD with unknown origin, because one cannot figure out the specific signs for subtelomeric rearrangements. Sequentially use of MLPA and FISH is a more efficient and economic method to detect the subtelomeric rearrangements.
Keywords:
本文献已被 维普 万方数据 PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号