Sauter S, Miterski B, Klimpe S, Bönsch D, Schöls L, Visbeck A, Papke T, Hopf H C, Engel W, Deufel T, Epplen J T, Neesen J
Institute of Human Genetics, University of Göttingen, Göttingen, Germany.
Hum Mutat. 2002 Aug;20(2):127-32. doi: 10.1002/humu.10105.
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.
遗传性痉挛性截瘫（HSP）是一组在遗传和临床方面具有异质性的神经退行性疾病，其特征为下肢进行性痉挛和反射亢进。与2号染色体p臂连锁的常染色体显性遗传性痉挛性截瘫4型（SPG4）是常染色体显性遗传性痉挛性截瘫最常见的形式。它是由编码痉挛蛋白（一种ATP酶的AAA蛋白家族成员）的SPG4基因突变引起的。在本研究中，对来自德国161个明显无亲缘关系家庭的HSP患者的痉挛蛋白基因进行了分析。作者在161个HSP家庭中的27个家庭中鉴定出了突变；其中23个突变此前未被描述过，且仅在两个家庭中发现了一个相同的突变。在检测到的突变中，有14个移码突变、4个无义突变、4个错义突变、一个跨越几个外显子的大片段缺失，以及4个影响剪接的突变。大多数新突变位于痉挛蛋白基因保守的AAA盒编码区域。在一组未经选择的德国HSP患者中，痉挛蛋白基因突变的相对频率约为17%。移码突变在该人群的SPG4突变中占大多数。剪接突变的比例远低于其他地方的报道。
