Sotos综合征的研究进展  

Progress of research on Sotos syndrome

作　　者：王新宁[1] 魏珉[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院儿科,北京100005

出　　处：《国际遗传学杂志》2010年第3期184-187,共4页International Journal of Genetics

基　　金：基金项目：国家重点基础研究发展计划（973计划）（2005CB522507） 通信作者：魏珉（E-mail：[e-mail]）

摘　　要：Sotos综合征（MIM#117550）是一种以儿童期过度生长现象为特征的遗传病，主要表现为巨头畸形、特殊面容、骨龄提前以及不同程度的发育迟缓。目前已有数百名病例报道，具体发病率不详。约75％的病例是由NSD1基因内点突变或5,t35微缺失所导致，欧裔患者多由5q35微缺失引起，而约50％日本患者主要由基因内点突变引起，仍有约25％病例未检测出NSD1基因异常，其具体致病机制尚不完全清楚。NSD1基因定位于染色体5q35，此基因编码一种组蛋白甲基化酶，该酶与转录调节过程有关。通过FISH（fluorescent in situ hybridization）分析、MLPA（multiplex ligation—dependent probe amplification）及实时定量荧光PCR反应等技术可以检测NSD1基因整体或部分缺失，直接测序可以检测出NSD1基因点突变。绝大部分NSDI基因异常为新生突变，多数为散发病例，但也发现数例家族性遗传病例。本病鉴别诊断主要为以生长过度为特征的疾病，包括Weaver综合征，Beckwith—Wiedeman综合征，脆性x染色体综合征等。目前本病尚无理想疗法，主要为对症治疗。出生后第一年内儿科随访对于本病临床并发症如脊柱侧弯及热性癫痫发作的治疗和预防监测有重要意义。Sotos syndrome（MIM#117550） is an inherited disease characterized by overgrowth in childhood. The cardinal features are macrocephaly, distinctive facial features, advanced bone age and mental retardation. Hundreds of Sotos cases have been reported so far, but the concrete incidence is not known. Sotos syndrome results from mutations and deletions of the NSD1 gene, located at chromosome 5q35. The NSD1 gene encodes the nuclear receptor-binding SET domain-containing protein 1, which is related to the modulation of transcription. About 75% of patients with Sotos sydrome are caused by NSD1 intragenic mutations or microdeletions. The majority of non-Japanese cases of Sotos are caused by NSD1 point mutation, while microdeletions account for about 50% of Japanese patient populations. No genetic abnormalities were found in nearly 25% of cases of Sotos. The accurate pathogenic reason of these cases remain unknown. Point mutations and microdeletions could be detected through direct sequencing, FISH analysis, MLPA and real-time quantitive fluorescent PCR. Most of the mutations are novel ones, most of cases are sporadic and several familial cases were reported. The differential diagnosis of Sotos are those characterised by excessive growth, such as Weaver Syndrome, Beckwith-Wiedemann Syndrome and Fragile-X Syndrome. No ideal therapies aim at Sotos now and symptomatic treatment is the main method to alleviate clinical symptoms. Follow-up in the first year after birth is of great significant for preventing and monitoring clinical complications, including scoliosis, febrile seizure and learning disability and so on.

关 键 词：Sotos生长过度 NSD1基因 基因型与表型 

分 类 号：R72[医药卫生—儿科]