Hedera P, DiMauro S, Bonilla E, Wald J, Eldevik O P, Fink J K
Department of Neurology, University of Michigan, Ann Arbor, USA.
Neurology. 1999 Jul 13;53(1):44-50. doi: 10.1212/wnl.53.1.44.
To describe clinical, electrophysiologic, neuroimaging, and muscle biopsy features in a hereditary spastic paraplegia (HSP) kindred linked to a new HSP locus on chromosome 8q.
HSP is a genetically diverse group of disorders characterized by insidiously progressive spastic weakness in the legs. We recently analyzed a Caucasian kindred with autosomal dominant HSP and identified tight linkage to a novel HSP locus on chromosome 8q23-24.
Clinical analysis, nerve conduction studies, electromyography, somatosensory evoked potentials, MRI of brain and spinal cord, and muscle biopsy for mitochondrial analysis were performed in members of the first HSP kindred linked to chromosome 8q.
Fifteen individuals showed insidiously progressive spastic paraparesis beginning between ages 22 and 60 years (average, 37.2 years). Spinal cord MRI in 1 moderately affected subject showed significant atrophy of the thoracic spinal cord as determined by cross-sectional area measurements. Somatosensory evoked potential recording, electromyography, nerve conduction studies, and muscle biopsy, including histochemical and biochemical analysis of mitochondrial function, were normal.
The phenotype in this family is that of typical, but severe, uncomplicated HSP. Other than apparently increased severity, there were no clinical features that distinguished this family from autosomal dominant HSP linked to loci on chromosomes 2p, 14q, and 15q. This clinical similarity between different genetic types of autosomal dominant HSP raises the possibility that genes responsible for these clinically indistinguishable disorders may participate in a common biochemical cascade. Normal results of muscle histochemical and biochemical analysis suggest that mitochondrial disturbance, a feature of chromosome 16-linked autosomal recessive HSP due to paraplegin gene mutations, is not a feature of chromosome 8q-linked autosomal dominant HSP and may not be a common factor of HSP in general.
描述与8号染色体q臂上一个新的遗传性痉挛性截瘫（HSP）基因座相关的一个HSP家系的临床、电生理、神经影像学和肌肉活检特征。
HSP是一组遗传异质性疾病，其特征为隐匿性进展的腿部痉挛性无力。我们最近分析了一个患有常染色体显性HSP的白人家系，并确定其与8号染色体q23 - 24上一个新的HSP基因座紧密连锁。
对与8号染色体q臂相关的首个HSP家系的成员进行了临床分析、神经传导研究、肌电图检查、体感诱发电位检测、脑和脊髓的MRI检查以及用于线粒体分析的肌肉活检。
15名个体表现出隐匿性进展的痉挛性截瘫，起病年龄在22岁至60岁之间（平均37.2岁）。1名中度受累患者的脊髓MRI显示，通过横截面积测量确定胸段脊髓有明显萎缩。体感诱发电位记录、肌电图检查、神经传导研究以及肌肉活检（包括线粒体功能的组织化学和生化分析）均正常。
该家系的表型为典型但严重的、无并发症的HSP。除了严重程度明显增加外，没有临床特征可将该家系与与2号染色体p臂、14号染色体q臂和15号染色体q臂上基因座相关的常染色体显性HSP区分开来。不同遗传类型的常染色体显性HSP之间的这种临床相似性增加了以下可能性，即导致这些临床难以区分的疾病的基因可能参与一个共同的生化级联反应。肌肉组织化学和生化分析结果正常表明，线粒体功能障碍是由截瘫蛋白基因突变导致的与16号染色体连锁的常染色体隐性HSP的一个特征，但不是与8号染色体q臂连锁的常染色体显性HSP的特征，也可能不是一般HSP的常见因素。
