脊髓性肌萎缩症表型及相关基因的研究进展

Research progress in phenotypes and related genes of spinal muscular atrophy

脊髓性肌萎缩症(SMA)是常见的神经肌肉系统常染色体隐性遗传病,运动神经元存活基因1(SMN1)为其致病基因。目前多项研究表明该病为多系统受累疾病,除了神经肌肉系统外,还包括心血管系统、消化系统、代谢系统、泌尿生殖系统等。患者临床表现多样、致病突变相同表明其存在遗传及环境修饰因子等因素影响,如运动神经元存活基因2拷贝数、神经细胞凋亡抑制蛋白基因拷贝数、锌指蛋白1及网质3蛋白过度表达、神经钙蛋白δ表达下调均能修饰表型。可为遗传咨询和预后评估提供参考,可以作为新的治疗靶点。该文将对SMA多系统受累情况及修饰基因研究进展作一综述。

Spinal muscular atrophy(SMA)is a common autosomal recessive hereditary disease of the neuromuscular system,and the survival motor neuron 1(SMN1)gene is its pathogenic gene.At present,a number of studies have shown that SMA is a disease involving multiple systems,including the cardiovascular system,the digestive system,the metabolic system and the genitourinary system besides the neuromuscular system.The fact that the patients with the diversity of clinical manifestations and the same pathogenic mutations indicates that there were genetic and environmental modifying factors,such as the copy number of survival motor neuron 2,the copy number of neuronal apoptosis inhibitory protein,the over expressions of zinc finger protein 1 and plastin 3 protein,and down-regulation of neurocalcin delta protein,which all can modify the phenotypes.It can provide reference for genetic counseling and prognosis evaluation,and can be used as new therapeutic targets.In this paper,the research progress of the multi-system involvement of SMA and modifier genes is reviewed.