摘要
目的探讨脊髓性肌萎缩症（spinalmuscularatrophy，SMA）患儿运动神经元生存基因1（survivalmotorneuron1，SMNj）向SMN2基因的转化及其与临床表型的关系。方法对417例SMNl第7外显子纯合缺失的患儿，应用聚合酶链反应-限制性片段长度多态方法筛查SMNl第8外显子是否纯合缺失，并通过基因组测序、多重连接探针扩增以及克隆测序等方法进行转化基因类型的研究和验证。结果在417例患儿中，31例（7．4％）未发现第8外显子纯合缺失，基因组测序等实验证实这些患者均携带SMNl／SMNZ融合基因。根据基因互换的位置，共存在5种不同的转化类型：SMN2-17b／SMNlE8、sMN2-17a／SMNl17b、SMN2-E7／SMNl17a、SMNl16／SMN2E1／sMNlITa以及SMN2-E7／SMNl17a／SMN217b。SMN基因转化在I型～Ⅲ型患儿中均存在，10例经转化后SMN2拷贝数为3的I型～Ⅲ型患儿的平均生存年龄为5岁4月。结论中国SMA人群中存在SMNl基因的部分转化，并在一定程度上影响了患儿（尤其是I型）的生存。
Objective To investigate the type and frequency of gene conversion from SMN1 to SMN2 in Chinese patients affected with spinal muscular atrophy（SMA）, and to explore the relationship between gene conversion and clinical phenotype. Methods Non-homozygous deletion of SMN1 gene exon 8 was screened among 417 patients with SMN1 exon 7 homozygous deletions. To analyze and verify the types of gene conversion, genomic DNA sequencing, multiplex ligation-dependent probe amplification （MLPA）, and gene subcloning and sequencing were carried out. Results Thirty-one patients （7.4% of all） with non- homozygous deletions of SMN1 exon 8 were detected. Through series of experiments, the fusion genes SMN1/SMN2 in all cases were delineated. Five types of gene conversions were identified, which included SMN2-I7b/ SMN1 E8, SMN2-I7a/ SMN1 I7b, SMN2-E7/ SMN1 I7a, SMN1 I6/ SMN2 ET/ SMN1 I7a and SMN2-ET/ SMN1 I7a/ SMN2 I7b. Such conversions were found in the type I-Ill patients. For 10 patients with type I -III SMA and 3 copies of SMN2 gene produced by conversion, the average survival age was 5 year and 4 months. Conclusion Partial conversions of SMN1 gene have been found among Chinese SMA patients. The type of conversion and frequency seem to be different from those of other races. Gene conversion to some extent may impact on survival time and rate of SMA patients, especially type I SMA.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2011年第6期606-611,共6页
Chinese Journal of Medical Genetics
基金
基金项目：国家自然科学基金（81050034）
北京市自然科学基金（7112020）
