Abel Annette, Fonknechten Nuria, Hofer Anne, Dürr Alexandra, Cruaud Corinne, Voit Thomas, Weissenbach Jean, Brice Alexis, Klimpe Sven, Auburger Georg, Hazan Jamilé
Molecular Genetics Section, Clinic for Neurology, JW Goethe University, House 26, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Neurogenetics. 2004 Dec;5(4):239-43. doi: 10.1007/s10048-004-0191-2. Epub 2004 Oct 28.
Hereditary spastic paraplegia (HSP) is a group of neurodegenerative disorders mainly characterized by progressive spasticity of the lower limbs. The major features of HSP are a marked phenotypic variability both among and within families and an extended genetic heterogeneity. More than 20 HSP loci and 10 spastic paraplegia genes (SPG) have been identified to date, including the genes responsible for the two most frequent forms of autosomal dominant spastic paraplegia (AD-HSP), encoding spastin (SPG4) and atlastin (SPG3A), respectively. To date, only eight mutations have been described in the atlastin gene, which was reported to account for about 10% of all AD-HSP families. We investigated 15 German and French AD-HSP families, including the 3 large pedigrees that allowed the mapping and subsequent refinement of the SPG3A locus. Three novel mutations were found in exons 4, 9, and 12 of the atlastin gene and the common R239C mutation located in exon 7 was confirmed in a 7th family of European origin. Overall, the comparison of the clinical data for all SPG3A-HSP families reported to date failed to reveal any genotype/phenotype correlation as demonstrated for other forms of AD-HSP. However, it confirmed the early onset of this form of HSP, which was observed in almost all affected individuals with a mutation in the atlastin gene.
遗传性痉挛性截瘫（HSP）是一组神经退行性疾病，主要特征为下肢进行性痉挛。HSP的主要特点是家族间和家族内存在显著的表型变异性以及广泛的遗传异质性。迄今为止，已确定了20多个HSP基因座和10个痉挛性截瘫基因（SPG），包括分别负责两种最常见的常染色体显性遗传性痉挛性截瘫（AD - HSP）形式的基因，它们分别编码spastin（SPG4）和atlastin（SPG3A）。迄今为止，atlastin基因中仅描述了8种突变，据报道该基因约占所有AD - HSP家族的10%。我们研究了15个德国和法国的AD - HSP家族，包括3个大型家系，这些家系有助于对SPG3A基因座进行定位并随后进行精细定位。在atlastin基因的外显子4、9和12中发现了3种新突变，并且在第7个欧洲血统的家族中证实了位于外显子7中的常见R239C突变。总体而言，对迄今为止报道的所有SPG3A - HSP家族的临床数据进行比较，未能揭示出如其他形式的AD - HSP所显示的任何基因型/表型相关性。然而，它证实了这种形式的HSP发病较早，几乎在所有atlastin基因突变的受影响个体中都观察到了这一点。
