Clinical and genetic study of SPG6 mutation in a Chinese family with hereditary spastic paraplegia

• Published in: Journal of the neurological sciences Vol. 266; no. 1; pp. 109 - 114
• Main Authors: Liu, Shi Guo, Zhao, Jian Jun, Zhuang, Mao You, Li, Fei Feng, Zhang, Qing Jun, Huang, Shang Zhi, Che, Feng Yuan, Lu, De Guo, Liu, Shi En, Teng, Ji Jun, Ma, Xu
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 15.03.2008; Elsevier Science
• Subjects: Action Potentials - physiology; Adolescent; Adult; Age of Onset; Aged; Biological and medical sciences; China; Diseases of striated muscles. Neuromuscular diseases; DNA - genetics; Electromyography; Electrophysiology; Evoked Potentials, Motor - physiology; Female; Genotype; Genotype–phenotype; Humans; Lod Score; Magnetic Resonance Imaging; Male; Medical sciences; Membrane Proteins - genetics; MEP; Middle Aged; MRI; Mutation - genetics; Mutation - physiology; Neural Conduction - physiology; Neurology; NIPAI; Pedigree; Phenotype; Spastic Paraplegia, Hereditary - genetics; Spastic Paraplegia, Hereditary - pathology; SPG6; Spinal Cord - pathology; China; NIPAI; MEP; SPG6; Genotype–phenotype; MRI; Nervous system diseases; Genotype; Nuclear magnetic resonance imaging; Genetic disease; Cerebral disorder; Genotype-phenotype; Hereditary spastic paraplegia; Phenotype; Central nervous system disease; Chinese; Degenerative disease; Mutation; Spinal cord disease
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/j.jns.2007.09.024

Abstract Mutations in the NIPA1 gene cause autosomal dominant hereditary spastic paraplegia (ADHSP). To date, little is known about the relationship between genotype–phenotype correlation. In order to examine the gene mutation associated with the genotype–phenotype of Chinese kindred with ADHSP, linkage analysis and mutation detection were performed. For affected family members, clinical analysis, electrophysiological examination and MRI of the brain and spinal cord were also performed. Every effected patient had a c316 (G106R) mutation in the NIPA1 gene. Neurophysiological examination revealed decreased amplitude of compound muscle action potentials (CMAP) from the tibial and peroneal motor nerves in most patients. Sensory nerve action potential (SNAP) from the tibialis nerve was not elicited in most patients. Central motor conduction time (CMCT) to the abductor pollicis brevis muscle (APB), first metatarsal interosseus muscle (FMI) and anterior tibial muscle (AT) were either absent or clearly prolonged in all patients. Spinal cord MRI showed different levels of atrophy in every affected individual. These lesions present an increased spot or patch signal on transverse axis T2WI and an intense signal of continual longitudinal strip on the anteroposterior axis. Our study supports that mutations in the NIPA1 gene cause ADHSP and further demonstrates genotype–phenotype correlations in SPG6.