Alber Burkhard, Pernauer Magdalena, Schwan Annemarie, Rothmund Gabriele, Hoffmann Karl T, Brummer Dagmar, Sperfeld Anne D, Uttner Ingo, Binder Heinrich, Epplen Joerg T, Dullinger Jörn, Ludolph Albert C, Meyer Thomas
Department of Neurology, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
J Neurol Sci. 2005 Sep 15;236(1-2):9-12. doi: 10.1016/j.jns.2005.03.040.
Thin corpus callosum has been recently observed in two patients with an autosomal dominant trait of hereditary spastic paraplegia (HSP) linked to a novel mutation in the spastin gene (SPG4). In the same two patients cerebellar atrophy has been found. Reportedly, in other members of the same family, there has been a variable presence of mental retardation. We report on the clinical and genetic investigation of an Austrian family with a novel mutation in the spastin gene. Genetic analysis of the SPG4 locus revealed a mutation (C1120A) and a known intronic polymorphism (996-47G>A) of the spastin gene. In one affected family member, previously undescribed dysplasia of the corpus callosum (CC) was found in conjunction with otherwise uncomplicated HSP. Dysplastic CC was not paralleled with cortical atrophy, cognitive impairment or other phenotypic variations. Two further affected family members showed the same mutation and polymorphism, but no evidence of CC abnormalities. We conclude that apparently pure HSP may present with MRI features of dysplastic CC. This finding extended the spastin-related phenotype which is distinct from previous reports of thin CC in HSP.
最近在两名患有与痉挛蛋白基因(SPG4)新突变相关的常染色体显性遗传痉挛性截瘫(HSP)的患者中观察到胼胝体变薄。在这两名患者中还发现了小脑萎缩。据报道,在同一家族的其他成员中,存在不同程度的智力迟钝。我们报告了一个患有痉挛蛋白基因新突变的奥地利家族的临床和基因研究。对SPG4位点的基因分析揭示了痉挛蛋白基因的一个突变(C1120A)和一个已知的内含子多态性(996-47G>A)。在一名受影响的家族成员中,发现了以前未描述过的胼胝体发育异常(CC),同时伴有无并发症的HSP。发育异常的CC与皮质萎缩、认知障碍或其他表型变异无关。另外两名受影响的家族成员显示出相同的突变和多态性,但没有CC异常的证据。我们得出结论,明显单纯的HSP可能表现出MRI上发育异常的CC特征。这一发现扩展了与痉挛蛋白相关的表型,这与之前关于HSP中CC变薄的报道不同。