Warnecke T, Duning T, Schwan A, Lohmann H, Epplen J T, Young P
Department of Neurology, University Hospital of Münster, Münster, Germany.
Neurology. 2007 Jul 24;69(4):368-75. doi: 10.1212/01.wnl.0000266667.91074.fe.
Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous neurodegenerative disorder characterized by progressive spastic paraparesis of the lower limbs.
To identify the genotype and characterize the phenotype in a family with a novel form of complicated autosomal recessive hereditary spastic paraparesis (ARHSP).
Six subjects of a Turkish family were examined by clinical evaluation, detailed neuropsychological testing, neurophysiologic studies, MRI, diffusion tensor imaging (DTI), and mutation analysis of SPG7 gene.
Three individuals were affected by a juvenile-onset form of complicated ARHSP due to the missense mutation c.2075G>C in exon 15 of the SPG7 gene in the homozygous state, substituting serine with threonine at codon 692. As additional clinical features, cerebellar syndrome, supranuclear palsy, and cognitive impairment, particularly disturbance of attention and executive functions, were found. MRI showed cerebellar atrophy and mild frontal cerebral atrophy. DTI revealed bilateral disturbance of white matter integrity in corticospinal tracts, frontal lobes, and the midbrain.
The new SPG7 gene mutation leads to a novel complicated autosomal recessive hereditary spastic paraparesis phenotype that widens the spectrum of different brain systems that are optionally affected in hereditary spastic paraplegia (HSP). In this novel phenotype, spastic paraparesis is related to cerebral damage of corticospinal tracts. Impairment of attention and executive functions is due to white matter loss in frontal lobes. Furthermore, supranuclear palsy is caused by white matter damage in the midbrain. This multisystem affection, which was detected by the use of diffusion tensor imaging, may reflect a mitochondrial dysfunction that contributes to the underlying pathogenesis of SPG7-HSP.
遗传性痉挛性截瘫（HSP）是一种临床和基因异质性神经退行性疾病，其特征为下肢进行性痉挛性轻瘫。
鉴定一个患有新型复杂常染色体隐性遗传性痉挛性截瘫（ARHSP）家系的基因型并对其表型进行特征描述。
对一个土耳其家系的6名成员进行了临床评估、详细的神经心理学测试、神经生理学研究、MRI、弥散张量成像（DTI）以及SPG7基因的突变分析。
3名个体因SPG7基因第15外显子的错义突变c.2075G>C处于纯合状态，导致692密码子处的丝氨酸被苏氨酸替代，患青少年起病型复杂ARHSP。作为额外的临床特征，发现有小脑综合征、核上性麻痹和认知障碍，尤其是注意力和执行功能障碍。MRI显示小脑萎缩和轻度额叶脑萎缩。DTI显示双侧皮质脊髓束、额叶和中脑白质完整性受损。
新的SPG7基因突变导致一种新型复杂常染色体隐性遗传性痉挛性截瘫表型，拓宽了遗传性痉挛性截瘫（HSP）中可选择性受累的不同脑系统的范围。在这种新型表型中，痉挛性轻瘫与皮质脊髓束的脑损伤有关。注意力和执行功能障碍是由于额叶白质丢失。此外，核上性麻痹是由中脑白质损伤引起的。通过弥散张量成像检测到的这种多系统受累可能反映了线粒体功能障碍，这有助于SPG7-HSP的潜在发病机制。
