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Clinical, Epidemiological and Molecular Genetical Research for Spinal Muscular Atrophy

脊髓性肌萎缩症的临床、流行病学和分子遗传学研究

基本信息

批准号：
10670762
负责人：
SAITO Kayoko
金额：
$ 2.05万
依托单位：
TOKYO WOMEN'S MEDICAL UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670762/
关键词：
spinal muscular artophy clinicla classificaion gene analysis SMN gene NAIP gene gene deletion modifying gene clinical severity 脊椎性筋萎縮症疫学的検討臨床型と遺伝子型 DNAとmRNA 培養骨格筋細胞

项目摘要

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by degeneration of motor neurons of the spinal cord and muscular atrophy. SMA is caused by mutation of the survival motor neuron (SMN) gene. We conducted a molecular genetic analysis of SMA patients and compared clinical severity with deletions of the SMNt and neuronal apoptosis inhibitory protein (NAIP) genes, and C212 and C272 microsatellite markers. We analyzed the SMN and NAIP genes in 89 SMA families ; 30 type I, 29 type II and 30 type III. Using the multi-copy microsatellite C212 and C272 markers, we performed haplotype analysis in 41 familes ; 15 type I, 15 type II and 11 type III. We defined 0-2 copies/ 2 chromosomes as a deletion of he H4F5 gene.Seventy-eight cases (87.6%) showed deletion of both genes or only the SMN gene. A significantly higher proportion of type I patients had deletion of both genes (p<0.05). Cases who had deletion of both the SMN and NAIP genes showed significantly earlier onset of disease. There were six sibling pairs in our subjects. Disease severity in each sibling was comparable, but two sibling pairs showed different disease severity. Five type I cases had a broad deletion that spanned the H4F5, SMN and NAIP genes. A significantly higher proportion of type I subjects had this deletion.Twenty-four of 4l (58.5%) showed C272 deletion or C212 and C272 deletion in addition to deletion of the SMN gene. We determined the number of C212 alleles present on their chromosomes by haplotype analysis. A reduction of C212 alleles was found in 48% of type I (2 copies) and in 60-80% of type II and III (3 copies). A total of 60% of the control subjects showed 4 copies. These results suggested that type I patients had homozygous deletion of C212 and type II and III patiensts had deletion of C212 in one chromosome, which means compound heterozygosity.

脊髓性肌萎缩症（SMA）是一种常染色体隐性神经肌肉疾病，以脊髓运动神经元变性和肌肉萎缩为特征。SMA是由存活运动神经元（SMN）基因突变引起的。我们对SMA患者进行了分子遗传学分析，并比较了SMNt和神经元凋亡抑制蛋白（NAIP）基因缺失以及C212和C272微卫星标记的临床严重程度。我们分析了89个SMA家族的SMN和NAIP基因；I型30人，II型29人，III型30人。利用多拷贝微卫星C212和C272标记，对41个家族进行了单倍型分析；I型15个，II型15个，III型11个。我们将0-2拷贝/ 2条染色体定义为H4F5基因的缺失。78例（87.6%）同时缺失或仅缺失SMN基因。I型患者两种基因缺失的比例显著高于对照组（p<0.05）。同时缺失SMN和NAIP基因的患者发病时间明显提前。我们的研究对象中有六对兄弟姐妹。每个兄弟姐妹的疾病严重程度具有可比性，但两对兄弟姐妹显示不同的疾病严重程度。5例I型患者的H4F5、SMN和NAIP基因广泛缺失。I型受试者中有这种缺失的比例明显更高。除SMN基因缺失外，41例患者中有24例（58.5%）存在C272缺失或C212和C272缺失。我们通过单倍型分析确定了其染色体上存在的C212等位基因的数量。C212等位基因在48%的I型（2个拷贝）和60-80%的II型和III型（3个拷贝）中减少。60%的对照组显示了4份拷贝。这些结果表明，I型患者存在C212纯合缺失，II型和III型患者在一条染色体上存在C212缺失，即复合杂合性。