IDENTIFICATION AND CHARACTERIZATION OF A SPINAL MUSCULAR ATROPHY-DETERMINING GENE
IDENTIFICATION AND CHARACTERIZATION OF A SPINAL MUSCULAR ATROPHY-DETERMINING GENE
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DOI：
10.1016/0092-8674(95)90460-3
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发表时间：
1995-01-13
期刊：
影响因子：
64.5
通讯作者：
MELKI, J
中科院分区：
文献类型：
--
作者：
LEFEBVRE, S;BURGLEN, L;MELKI, J
脊髓性肌萎缩症（SMA）是一种常见的致死性常染色体隐性遗传疾病，其特征是下运动神经元变性，导致进行性瘫痪伴肌萎缩。SMA基因已定位于染色体5q13，其中已报告大规模缺失。在这里，我们描述了正常染色体中的500 kb元件的反向复制，并将端粒区域内的关键区域缩小到140 kb。该区间包含编码294个氨基酸的新蛋白质的20kb基因。一个高度同源的基因存在于95%的对照的着丝粒元件中。229例患者中有226例端粒基因缺失或中断，保留该基因的患者（229例中有3例）携带点突变（Y272C）或内含子6和7共有剪接位点的短缺失。这些数据表明，这个基因，称为运动神经元生存（SMN）基因，是一个SMA决定基因。
Spinal muscular atrophy (SMA) is a common fatal autosomal recessive disorder characterized by degeneration of lower motor neurons, leading to progressive paralysis with muscular atrophy. The gene for SMA has been mapped to chromosome 5q13, where large-scale deletions have been reported. We describe here the inverted duplication of a 500 kb element in normal chromosomes and narrow the critical region to 140 kb within the telomeric region. This interval contains a 20 kb gene encoding a novel protein of 294 amino acids. An highly homologous gene is present in the centromeric element of 95% of controls. The telomeric gene is either lacking or interrupted in 226 of 229 patients, and patients retaining this gene (3 of 229) carry either a point mutation (Y272C) or short deletions in the consensus splice sites of introns 6 and 7. These data suggest that this gene, termed the survival motor neuron (SMN) gene, is an SMA-determining gene.