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Compound heterozygous mutation in two unrelated cases of Chinese spinal muscular atrophy patients
Qu Yu-jin1; Song Fang1; Yang Yan-ling2; Jin Yu-wei1; Bai Jin-li1
关键词spinal muscular atrophy survival motor neuron gene 1 compound heterozygous mutation gene conversion
刊名CHINESE MEDICAL JOURNAL
2011-02-05
DOI10.3760/cma.j.issn.0366-6999.2011.03.012
124期:3页:385-389
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, General & Internal
资助者National Natural Science Foundation of China ; Foundation of Capital Institute of Pediatrics ; National Natural Science Foundation of China ; Foundation of Capital Institute of Pediatrics
研究领域[WOS]General & Internal Medicine
关键词[WOS]MOLECULAR ANALYSIS ; MISSENSE MUTATION ; SMA PATIENTS ; GENE ; SMN1 ; IDENTIFICATION ; DELETIONS ; PCR ; SEVERITY ; PROTEIN
英文摘要

Background Infantile proximal spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder. Approximately 90%-95% cases of SMA result from homozygous deletion of survival motor neuron gene 1 (SMN1) and 5% cases are caused by compound heterozygous mutation (a SMN1 deletion on one allele and a subtle mutation on the other allele).

Methods In this research, two unrelated patients were clinically diagnosed according to the criteria of proximal SMA. Genetic diagnosis was performed to detect the homozygous deletion of exon 7 of SMN1 by PCR-restriction fragment length polymorphism (RFLP) and genomic sequencing. Multiplex ligation-dependent probe amplification (MLPA) analysis was carried out to measure copy numbers of SMN1, SMN2 and neuronal apoptosis inhibitor protein (NAIP) in the patients. Further sequencing of SMN1 allele-specific PCR (AS-PCR) and SMN1 clones were also performed to analyze the point mutation of SMN1 gene. Additionally, the pedigree analysis of these two families was carried out to identify the transmission of the mutation.

Results The inconsistent results using PCR-RFLP and genomic sequencing showed homozygous deletion of exon 7 of SMN1 and heterozygous deletion accompanied with a suspicious mutation in SMN1 gene, respectively. MLPA analysis of these two cases exhibited one SMN1 copy deletion. One identical c.863G > T (p.Arg288Met) mutation was found in two cases by sequencing the SMN1 clones, which confirmed that both cases were SMA compound heterozygotes. One case showed partial conversion to form hybrid SMN (SMN217/SMN1 E8) identified by clones sequencing and another case carrying 3 SMN2 implied complete conversion from SMN1 to SMN2.

Conclusion p.Arg288Met is more a disease-causing mutation than a polymorphism variation, and children with this mutation may have more severe phenotypes. Chin Med J 2011;124(3):385-389

语种英语
所属项目编号81050034 ; 10-B09
资助者National Natural Science Foundation of China ; Foundation of Capital Institute of Pediatrics ; National Natural Science Foundation of China ; Foundation of Capital Institute of Pediatrics
WOS记录号WOS:000287992400012
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被引频次:7[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59657
专题北京大学第一临床医学院_儿科
作者单位1.Capital Inst Pediat, Dept Med Genet, Beijing 100020, Peoples R China
2.Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China
推荐引用方式
GB/T 7714
Qu Yu-jin,Song Fang,Yang Yan-ling,et al. Compound heterozygous mutation in two unrelated cases of Chinese spinal muscular atrophy patients[J]. CHINESE MEDICAL JOURNAL,2011,124(3):385-389.
APA Qu Yu-jin,Song Fang,Yang Yan-ling,Jin Yu-wei,&Bai Jin-li.(2011).Compound heterozygous mutation in two unrelated cases of Chinese spinal muscular atrophy patients.CHINESE MEDICAL JOURNAL,124(3),385-389.
MLA Qu Yu-jin,et al."Compound heterozygous mutation in two unrelated cases of Chinese spinal muscular atrophy patients".CHINESE MEDICAL JOURNAL 124.3(2011):385-389.
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