一个遗传性痉挛性截瘫家系的临床特点与spastin基因突变分析

目的探讨遗传性痉挛性截瘫(hereditary spastic paraplegia,HSP)一家系的临床特点及其与spastin基因突变关系。方法对整个家系进行详细的临床检查,先证者和家系内另两例患者进行了肌电图检查,先证者还进行了胸髓核磁共振检查。应用聚合酶链反应结合DNA序列分析方法,检测该家系中先证者和其父亲spastin基因的突变情况。结果家族中所有患者具有遗传性痉挛性截瘫的典型表现,先证者胸髓核磁共振成像显示胸髓明显萎缩,PCR-DNA序列分析患者spastin基因的17个外显子均未发现有异常的突变。结论该HSP家系的患者具有典型的临床表现,并非spastin基因外显子突变所致。     

AAA ATP酶与遗传性痉挛性截瘫

遗传性痉挛性截瘫是一种具有高度临床和遗传异质性的神经系统变性性疾病.现已定位35型,17型致病基因已被克隆.其中呈显性遗传的第4型和呈隐性遗传的第7型是较常见的亚型.它们的致病基因分别编码蛋白spastin与paraplegin,二者同属于AAA ATP酶家族.现对研究较多的这两型进行综述,并借此反映该病近年来的研究进展.     

AAA ATP酶与遗传性痉挛性截瘫

遗传性痉挛性截瘫是一种具有高度临床和遗传异质性的神经系统变性性疾病.现已定位35型,17型致病基因已被克隆.其中呈显性遗传的第4型和呈隐性遗传的第7型是较常见的亚型.它们的致病基因分别编码蛋白spastin与paraplegin,二者同属于AAA ATP酶家族.现对研究较多的这两型进行综述,并借此反映该病近年来的研究进展.     

AAA ATP酶与遗传性痉挛性截瘫

遗传性痉挛性截瘫是一种具有高度临床和遗传异质性的神经系统变性性疾病.现已定位35型,17型致病基因已被克隆.其中呈显性遗传的第4型和呈隐性遗传的第7型是较常见的亚型.它们的致病基因分别编码蛋白spastin与paraplegin,二者同属于AAA ATP酶家族.现对研究较多的这两型进行综述,并借此反映该病近年来的研究进展.     

AAA ATP酶与遗传性痉挛性截瘫

遗传性痉挛性截瘫是一种具有高度临床和遗传异质性的神经系统变性性疾病.现已定位35型,17型致病基因已被克隆.其中呈显性遗传的第4型和呈隐性遗传的第7型是较常见的亚型.它们的致病基因分别编码蛋白spastin与paraplegin,二者同属于AAA ATP酶家族.现对研究较多的这两型进行综述,并借此反映该病近年来的研究进展.     

AAA ATP酶与遗传性痉挛性截瘫

遗传性痉挛性截瘫是一种具有高度临床和遗传异质性的神经系统变性性疾病.现已定位35型,17型致病基因已被克隆.其中呈显性遗传的第4型和呈隐性遗传的第7型是较常见的亚型.它们的致病基因分别编码蛋白spastin与paraplegin,二者同属于AAA ATP酶家族.现对研究较多的这两型进行综述,并借此反映该病近年来的研究进展.     

AAA ATP酶与遗传性痉挛性截瘫

遗传性痉挛性截瘫是一种具有高度临床和遗传异质性的神经系统变性性疾病.现已定位35型,17型致病基因已被克隆.其中呈显性遗传的第4型和呈隐性遗传的第7型是较常见的亚型.它们的致病基因分别编码蛋白spastin与paraplegin,二者同属于AAA ATP酶家族.现对研究较多的这两型进行综述,并借此反映该病近年来的研究进展.     

AAA ATP酶与遗传性痉挛性截瘫

遗传性痉挛性截瘫是一种具有高度临床和遗传异质性的神经系统变性性疾病.现已定位35型,17型致病基因已被克隆.其中呈显性遗传的第4型和呈隐性遗传的第7型是较常见的亚型.它们的致病基因分别编码蛋白spastin与paraplegin,二者同属于AAA ATP酶家族.现对研究较多的这两型进行综述,并借此反映该病近年来的研究进展.     

AAA ATP酶与遗传性痉挛性截瘫

遗传性痉挛性截瘫是一种具有高度临床和遗传异质性的神经系统变性性疾病.现已定位35型,17型致病基因已被克隆.其中呈显性遗传的第4型和呈隐性遗传的第7型是较常见的亚型.它们的致病基因分别编码蛋白spastin与paraplegin,二者同属于AAA ATP酶家族.现对研究较多的这两型进行综述,并借此反映该病近年来的研究进展.     

Spastin gene mutations in Bulgarian patients with hereditary spastic paraplegia

Hereditary spastic paraplegia (HSP) is an extremely heterogeneous group of neurodegenerative disorders affecting the longest axons in the central nervous system. The most common genetic form accounting for about 40% of the autosomal-dominant HSP (ADHSP) cases is spastin gene, SPG4. We performed mutation screening of the spastin gene on 36 unrelated HSP patients from three different ethnic groups (Bulgarian, Turks and Gypsies) and found four new mutations and one already reported. The phenotype-genotype correlations in Bulgarian SPG4 patients showed a great difference in the age at disease onset between patients with missense mutations and those harboring deletions and splice-site mutations. Our study is the first to present corroborative clinical data in favor of the general hypothesis that the clinical course of the disease is related to the type of the spastin mutation. The clinical and genealogical findings in Bulgarian SPG4 patients suggest that a positive family history for inheritance as an autosomal-dominant trait is a strong indication for spastin mutation screening.     

Mutation analysis of the spastin gene (SPG4) in patients in Germany with autosomal dominant hereditary spastic paraplegia

Hereditary spastic paraplegias (HSP) comprise a genetically and clinically heterogeneous group of neurodegenerative disorders characterized by progressive spasticity and hyperreflexia of the lower limbs. Autosomal dominant hereditary spastic paraplegia 4 linked to chromosome 2p (SPG4) is the most common form of autosomal dominant hereditary spastic paraplegia. It is caused by mutations in the SPG4 gene encoding spastin, a member of the AAA protein family of ATPases. In this study the spastin gene of HSP patients from 161 apparently unrelated families in Germany was analyzed. The authors identified mutations in 27 out of the 161 HSP families; 23 of these mutations have not been described before and only one mutation was found in two families. Among the detected mutations are 14 frameshift, four nonsense, and four missense mutations, one large deletion spanning several exons, as well as four mutations that affect splicing. Most of the novel mutations are located in the conserved AAA cassette-encoding region of the spastin gene. The relative frequency of spastin gene mutations in an unselected group of German HSP patients is approximately 17%. Frameshift mutations account for the majority of SPG4 mutations in this population. The proportion of splice mutations is considerably lower than reported elsewhere.     

Mutation analysis of the spastin gene (SPG4) in patients with hereditary spastic paraparesis

BACKGROUND—Hereditary spastic paraparesis is a genetically heterogeneous condition. Recently, mutations in the spastin gene were reported in families linked to the common SPG4 locus on chromosome 2p21-22.
OBJECTIVES—To study a population of patients with hereditary spastic paraparesis for mutations in the spastin gene (SPG4) on chromosome 2p21-22.
METHODS—DNA from 32 patients (12 from families known to be linked to SPG4) was analysed for mutations in the spastin gene by single strand conformational polymorphism analysis and sequencing. All patients were also examined clinically.
RESULTS—Thirteen SPG4 mutations were identified, 11 of which are novel. These mutations include missense, nonsense, frameshift, and splice site mutations, the majority of which affect the AAA cassette. We also describe a nucleotide substitution outside this conserved region which appears to behave as a recessive mutation.
CONCLUSIONS—Recurrent mutations in the spastin gene are uncommon. This reduces the ease of mutation detection as a part of the diagnostic work up of patients with hereditary spastic paraparesis. Our findings have important implications for the presumed function of spastin and schemes for mutation detection in HSP patients.


Keywords: spastin; hereditary spastic paraparesis; mutation; recessive     

遗传性痉挛性截瘫11型研究进展

遗传性痉挛性截瘫是一种遗传性、神经退行性变的疾病,具有明显的遗传异质性,遗传形式多样.遗传性痉挛性截瘫11型是隐形遗传尤其是合并有胼胝体发育不良患者中最常见的类型,现就近几年来该病的研究进展,从遗传性痉挛性截瘫11型的基因定位和克隆,基因突变情况及其临床表现,诊断与鉴别诊断、发病机制等方面进行全面的介绍.