Deletion analyses of SMN1 and NAIP genes in Malaysian spinal muscular atrophy patients
Deletion analyses of SMN1 and NAIP genes in Malaysian spinal muscular atrophy patients
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DOI：
10.1111/j.1442-200x.2007.02302.x
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发表时间：
2007-02-01
影响因子：
1.4
通讯作者：
Nishio, Hisahide
中科院分区：
文献类型：
--
作者：
Watihayati, Mohd S.;Zabidi-Hussin, Azhar M. H.;Nishio, Hisahide
背景：运动神经元存活基因1（SMN 1）被认为是脊髓性肌萎缩症（SMA）的致病基因，因为超过90%的SMA患者（无论其临床严重程度如何）均存在SMN 1基因的同源性缺失，而神经元凋亡抑制蛋白（NAIP）基因目前被认为是SMA严重程度的修饰因子。在马来西亚，它仍有待阐明是否SMN 1基因的缺失也是SMA的主要原因，或是否NAIP基因的缺失被发现在SMA patients.Methods：为了阐明SMA在马来西亚的发病机制，SMN 1和NAIP基因的缺失分析进行了24例马来西亚SMA患者。根据货车der Steege等人描述的方法进行SMN 1基因外显子7和8的缺失分析，结果：24例患者中19例（79%）存在SMN 1外显子7和外显子8的纯合性缺失。至于NAIP基因，24例患者中有6例（25%）检测到外显子5缺失。NAIP基因缺失与疾病的严重程度相关。结论：SMN 1外显子7的缺失是马来西亚SMA的主要原因，NAIP基因缺失在马来西亚的I型SMA中并不罕见。SMN 1基因缺失百分比较低可能是由于本研究纳入了一些无SMN 1基因异常的患者和/或一些SMN 1基因非缺失型突变的患者。
Background:The survival motor neuron 1 (SMN1) gene has been recognized to be responsible for spinal muscular atrophy (SMA) because it is homozygously deleted in more than 90% of SMA patients, irrespective of their clinical severity, whereas the neuronal apoptosis inhibitory protein (NAIP) gene is now considered to be a modifying factor of the severity of SMA. In Malaysia, it remains to be elucidated whether deletion of the SMN1 gene is also a main cause of SMA or whether deletion of the NAIP gene is found in the SMA patients.Methods:To clarify the pathogenesis of SMA in Malaysia, a deletion analysis of the SMN1 and NAIP genes was performed in 24 Malaysian SMA patients. Deletion analysis of exons 7 and 8 of the SMN1 gene was performed according to the method described by van der Steege et al., while deletion analysis of exon 5 of the NAIP gene was performed according to a method described by Roy et al.Results:Homozygous deletion of SMN1 exon 7 and exon 8 were identified in 19 out of 24 patients (79%). As to the NAIP gene, deletion of exon 5 was detected in six out of 24 patients (25%). NAIP gene deletion was correlated with severity of the disease.Conclusions: Deletion of the SMN1 exon 7 is a major cause of SMA in Malaysia, and NAIP gene deletions are not rare in type I SMA in Malaysia. The lower percentage of the SMN1 gene deletion may be due to the possibility that the present study included some patients without SMN1 gene abnormality and/or some patients with non-deletion type mutations in the SMN1 gene.