患有脊髓性肌萎缩症的个体中，神经元凋亡抑制蛋白基因存在部分缺失。

The gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy.

作者信息

Roy N, Mahadevan M S, McLean M, Shutler G, Yaraghi Z, Farahani R, Baird S, Besner-Johnston A, Lefebvre C, Kang X

机构信息

Molecular Genetics Laboratory, Children's Hospital of Eastern Ontario, Ottawa, Canada.

出版信息

Cell. 1995 Jan 13;80(1):167-78. doi: 10.1016/0092-8674(95)90461-1.

DOI:10.1016/0092-8674(95)90461-1

PMID:7813013

Abstract

The spinal muscular atrophies (SMAs), characterized by spinal cord motor neuron depletion, are among the most common autosomal recessive disorders. One model of SMA pathogenesis invokes an inappropriate persistence of normally occurring motor neuron apoptosis. Consistent with this hypothesis, the novel gene for neuronal apoptosis inhibitory protein (NAIP) has been mapped to the SMA region of chromosome 5q13.1 and is homologous with baculoviral apoptosis inhibitor proteins. The two first coding exons of this gene are deleted in approximately 67% of type I SMA chromosomes compared with 2% of non-SMA chromosomes. Furthermore, RT-PCR analysis reveals internally deleted and mutated forms of the NAIP transcript in type I SMA individuals and not in unaffected individuals. These findings suggest that mutations in the NAIP locus may lead to a failure of a normally occurring inhibition of motor neuron apoptosis resulting in or contributing to the SMA phenotype.

摘要

脊髓性肌萎缩症（SMA）以脊髓运动神经元缺失为特征，是最常见的常染色体隐性疾病之一。SMA发病机制的一种模型认为，正常发生的运动神经元凋亡存在不适当的持续状态。与该假设一致，神经元凋亡抑制蛋白（NAIP）的新基因已被定位于5号染色体q13.1的SMA区域，并且与杆状病毒凋亡抑制蛋白同源。与2%的非SMA染色体相比，该基因的两个起始编码外显子在约67%的I型SMA染色体中缺失。此外，逆转录聚合酶链反应（RT-PCR）分析显示，I型SMA个体中存在NAIP转录本的内部缺失和突变形式，而未受影响的个体中则没有。这些发现表明，NAIP基因座中的突变可能导致正常发生的运动神经元凋亡抑制失败，从而导致或促成SMA表型。