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脊髓性肌萎缩症SMN1和SMN2基因拷贝数变异分析 被引量:7

Copy number variation of SMN1 and SMN2 genes in spinal muscular atrophy and analysis of its clinical significance
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摘要 目的探讨运动神经元存活(SMN)1和SMN2基因拷贝数变异与脊髓性肌萎缩症(SMA)患儿临床表型的关系。方法以2011年10月至2012年12月在复旦大学附属儿科医院临床诊断SMA患儿为研究对象,采用基因组DNA多重连接探针扩增(MLPA)技术进行SMN1基因缺失和SMN2基因拷贝数变异检测,探讨拷贝数变异与SMA临床分型的关系。结果 41例临床诊断SMA患儿行基因检测,其中SMN1基因第7和(或)8外显子缺失37例(90.2%)进入分析,男女之比为1∶0.8,发病年龄为(7.5±7.0)个月。Ⅰ型20例(54.1%),Ⅱ型15例(40.5%),Ⅲ型2例(5.4%),发病年龄分别为(2.9±1.8)、(10.7±1.9)和(30.0±8.5)个月。37例SMN1基因第7和(或)8外显子缺失患儿中,18例SMN2基因第7和8外显子拷贝数为2个,其中13例(72.2%)为Ⅰ型,5例(27.8%)为Ⅱ型;19例SMN2基因第7和8外显子拷贝数增加(拷贝数3或4),其中7例(36.8%)为Ⅰ型,10例(52.6%)为Ⅱ型,2例(10.5%)为Ⅲ型,两组差异有统计学意义。5例患儿父母行SMN1基因检测,共检出杂合缺失9例,其中4例患儿父母均为SMN1基因第7和8外显子杂合缺失,1例患儿父亲为SMN1基因第7和8外显子杂合缺失,母亲未检测到纯合或杂合缺失。结论 SMN1基因第7和(或)8外显子纯合缺失是SMA致病主要原因,SMN2基因拷贝数增加与SMA表型严重程度呈负相关。 Objective To study the relation between phenotype of spinal muscular atrophy ( SMA ) in children and copy number variation of SMN1 and SMN2 gene. Methods Using genomic DNA multiplex ligation-dependent probe amplification (MLPA) the copy number variations of exon 7 and 8 of SMN1 and SMN2 were detected in children with clinically suspected SMA samples in Children's Hospital of Fudan University. Genotype and phenotype data were analyzed. Results The study covered 41 cases of children with suspected SMA. It included 37 cases (90.2%) with deletion of exon 7 and/or 8 of SMN1 gene, the ratio of male to female was 1 to 0.8, the average age of onset was (7.5± 7.0) months. There were type Ⅰ 20 cases (54.1%), type Ⅱ 15 cases (40.5%), type m 2 cases (5.4%), the average age of onset of type I was (2.9±1.8) months, type Ⅱ ( 10.7± 1.9) months and type Ⅲ ( 30. 0± 8.5 ) months. In 37 patients with deletions in SMN1 gene, exon 7 and/or 8 had 2 copies in SMN2 gene in 18 cases, the average age of onset was (4.9 ± 3.9) months. 13 out of 18 cases (72.2%) were type I , 5 cases (27. 8% ) were type Ⅱ. There were 19 patients with increased SMN2 gene copy number (3 or 4), the average age of onset was (9.9 ±8.5) months, 7 of 19 cases (36.8%) were type Ⅰ , 10 cases (52.6%) were type Ⅱ , 2 cases (10.5%) were type m. The parents of 5 cases were performed SMN1 gene detection, heterozygous deletion were found in 9 parents, deletions of exon 7 and 8 were found in 8 parents. In the rest one case, the father was found to be a carrier of deletion of exon 7 and 8, however the mother was a non-carrier. Conclusions Gene SMN1 exon 7 and/or 8 homozygous deletion mutation was the direct cause of SMA. SMN2 copy number increase was negatively correlated with the severity of the SMA phenotype.
出处 《中国循证儿科杂志》 CSCD 2013年第3期216-219,共4页 Chinese Journal of Evidence Based Pediatrics
关键词 脊肌萎缩症 SMN1基因 SMN2基因 拷贝数变异 Spinal muscular atrophy SMN1 gene SMN2 gene Copy number variation
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  • 1王旭,邹丽萍,方方,肖静,丁昌红,宋昉.运动神经元存活基因与儿童期脊肌萎缩症临床特征研究[J].临床儿科杂志,2005,23(5):275-277. 被引量:6
  • 2李文磊,丁新生,吴婷,姚娟,邓晓萱.脊髓性肌萎缩症基因诊断[J].中华神经科杂志,2005,38(7):426-429. 被引量:2
  • 3杨晓苏,邓益东,肖波,罗新明.儿童型脊肌萎缩症SMN基因缺失与微突变检测[J].中国当代儿科杂志,2005,7(6):489-492. 被引量:3
  • 4Russman BS. Spinal muscular atrophy: clinical classification and disease heterogeneity. J Child Neurology, 2007, 22:946-951. 被引量:1
  • 5Lefbvre S, Burglen L, Reboullet S, et al. Identification and characterization of a spinal muscular atrophy determing gene. Cell, 1995,80 : 155-165. 被引量:1
  • 6Munsat TM, davies KE. Meeting report: international SMA consortium meeting. Neuromuscul Disord, 1992,2 ( 5/6 ) : 423- 428. 被引量:1
  • 7Thieme A, Mitulla B, Schulze F, et al. Epidemiological data on Werdning- Hoffmann disease in Germany (West-Thttringen). Hum Genet, 1993, 91: 295-297. 被引量:1
  • 8Wirth B. An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA). Hum Mutat, 2000, 15:228-237. 被引量:1
  • 9Kesari A, Misra UK, Kalita J, et al. Study of suevival of motor neuron(SMN) and neuronal apoptosis inhibitory protein (NAIP) gene deletions in SMA patients. J Neurol, 2005, 252:667-671. 被引量:1
  • 10al-Rajeh S, Majumdar R, Awada A, et al. Application of DNA-dased tests for diagnosis of spinal muscular atrophy in Saudi Arabia. East Medterr Health J ,1999, 5 : 1225-1229. 被引量:1

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