中国脊髓性肌萎缩症患儿的SMN基因学研究

Study of SMN gene in Chinese children with spinal muscular atrophy

摘要:

目的：明确中国人各型脊髓性肌萎缩症(SMA)患儿SMN1基因外显子7和8缺失，SMN基因转变及微小突变情况。方法：对106例患者，采用PCR-RFLP检测基因缺失，RFLP筛查基因转变，并对PCR产物进行测序分析。基因转变率比较采用Fisher精确检验法进行统计学分析。结果：SMA患儿纯合SMN1外显子7和/或8缺失比率为91.5%，发现1例SMA中存在SMN1外显子7保留，而SMN1非编码外显子8缺失。在SMN1外显子7缺失而无外显子8缺失的患者中，各型间基因转变率差别无统计学意义，在SMN1外显子7缺失的SMA中，其基因转变率为8.3%。SMN第7外显子附近未发现基因微小突变。结论：SMN1基因外显子7和/或8缺失为中国SMA患儿的主要病因。SMA中存在SMN基因转变现象。SMN1基因外显子8的单独缺失可能致病。SMN1基因外显子7附近可能不是此病微小突变的热点区域。［中国当代儿科杂志，2010，12（7）：539-543］

Abstract:

OBJECTIVE: To study the incidence of homozygous absence of SMN1 exons 7 and 8, SMN gene conversion frequency and SMN subtle mutations in children with spinal muscular atrophy (SMA). METHODS: The homozygous deletion was detected by PCR-RFLP in 106 Chinese children with SMA, gene conversion by RFLP and subtle mutations by sequencing. RESULTS: The rate of deletion of SMN1 exons 7 and/or 8 was 91.5%. Deletion of SMN1 exon 8 but existence of exon 7 was noted in one child with SMA. There were no significant differences in the gene conversion frequency among children with different types of SMA and who had homozygous deletion of SMN1 exon 7 but existence of exon 8. The gene conversion frequency was 8.3% in children with homozygous deletion of SMN1 exon 7. No subtle mutations were found around SMN1 exon 7. CONCLUSIONS: Deletion of SMN1 exons 7 and/or 8 is the main cause of SMA in Chinese children. There exists a SMN gene conversion phenomenon in SMA. Deletion of exon 8 might lead to SMA. The hot area of subtle mutations of this disease might not be around SMN1 exon 7. ［Chin J Contemp Pediatr, 2010, 12 (7):539-543］