SPG4基因的遗传学研究

遗传性痉挛性截瘫(hereditary spastic paraplegia,HSP),又称为家族性Strümpell-Lorrain病,是一种具有临床及遗传高度异质性的神经系统遗传病,患病率为2/10万～9.6/10万,表现为缓慢进展的双下肢无力及痉挛性截瘫.根据遗传方式不同HSP可分为常染色体显性遗传、常染色体隐性遗传和X-连锁隐性遗传,以常染色体显性遗传最常见.目前已经发现40个HSP基因位点,已克隆19个疾病基因.其中spastin基因突变所致的遗传性痉挛性截瘫4型(spastic paraplegia-4,SPG4)约占常染色体显性遗传的HSP的40%.基因检测是诊断该病的金标准,有助于早期诊断、症状前诊断及产前诊断.动物模型的研究对揭示HSP的分子病理机制有重要作用,本文就SPG4基因的遗传学研究作一概述.

Advances of genetic research on the SPG4 gene

The hereditary spastic paraplegia (HSP), also known as Strümpell-Lorrain familial spasmodic paraplegia, is a highlighted clinical and genetic heterogeneity disorder with the prevalence of (2-9.6)/100,000. This disorder is characterized by progressive, usually severe spasticity and pyramidal weakness, predominantly in the lower limbs. Inheritance of this disease has been reported to be autosomal dominant (AD), autosomal recessive (AR), or X-linked recessive (XR), with the AD forms of HSP (ADHSP) being the most common type. At least 40 HSP gene loci have been localized and 19 genes have been identified. Forty percent of HSP cases are caused by mutations in the spastin (spastic paraplegia-4, SPG4) gene. Genetic diagnosis, the gold standard for diagnosis of the disease, may contribute to early diagnosis, presymptomatic diagnosis and prenatal diagnosis. The study of animal models plays an important role in revealing the molecular pathological mechanism of HSP. The known genetic research advances of the SPG4 gene are reviewed in this article.