Abstract

Proximal spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease caused by homozygous deletion in the seventh exon of the SMN1 gene. The aim of this work is to analyze the association of the allelic polymorphism of telomeric genes SMN1 and NAIP and the centromeric gene SMN2 of the 5q13 region with the clinical phenotype of SMA. It was shown that the homozygous genotype, which contains a telomeric deletion, covering both SMN1 and NAIP, is significantly more often observed in patients with the most severe type of SMA. Three or more copies of SMN2 are associated with a milder phenotype; the number of SMN2 copies affects the SMA phenotype more heavily than the length of the telomeric deletion. It was shown that one SMN2 copy is significantly more frequent than three or more copies of this gene in SMA-patients with homozygous deletion of SMN1 and NAIP. This fact may indicate the presence of a large deletion of all the three studied genes in SMA genotypes associated with the most severe type of SMA. It is noted that congenital SMA (type 0) is significantly less common in female patients, which may indicate the presence of SMA modifier genes on the X-chromosome.

中文翻译：

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脊髓性肌萎缩症表型的遗传修饰符

摘要

近端脊髓性肌萎缩症（SMA）是由SMN1基因第七外显子纯合缺失引起的常染色体隐性神经退行性疾病。这项工作的目的是分析端粒基因的等位基因多态性的关联SMN1和NAIP和着丝粒基因SMN2与SMA的临床表型5q13区域。结果表明，在SMA最严重的患者中，更常见的是包含端粒缺失的纯合基因型，覆盖SMN1和NAIP。SMN2的三个或更多副本与较轻的表型相关；SMN2的数量与端粒缺失的长度相比，拷贝对SMA表型的影响更大。结果表明，在具有SMN1和NAIP纯合缺失的SMA患者中，一个SMN2拷贝比该基因的三个或更多拷贝的频率明显更高。这一事实可能表明存在与最严重的SMA类型相关的SMA基因型中所有三个研究基因的大量缺失。注意，先天性SMA（0型）在女性患者中明显较少见，这可能表明X染色体上存在SMA修饰基因。