Paraplegin gene analysis in hereditary spastic paraparesis (HSP) pedigreesin northeast England

Objective: To identify the frequency and characterize the phenotype of para plegin mutations in the hereditary spastic paraparesis (HSP) population in the northeast of England. Background: HSP is a disorder that shows both cli nical and genetic heterogeneity. To date, 13 loci have been associated with an HSP phenotype, with the causative gene having been identified in four o f these. Two autosomal genes have been identified, paraplegin and spastin, and two X-linked genes have been identified, L1CAM (cell adhesion molecule) and proteolipid protein. Methods: Thirty HSP pedigrees from the northeast of England were analyzed for mutation in each of the 17 exons of the parapl egin gene. Results: A single family with a paraplegin mutation was identifi ed in which the paraplegin mutation co-segregates with an HSP phenotype in an apparent dominant manner. The authors also describe frequent polymorphis m in the paraplegin gene in both the HSP and control populations, Conclusio n: Mutations in the paraplegin gene are not a common cause of HSP in the no rtheast of England. The phenotype of the paraplegin-related HSP family desc ribed had several striking features including amyotrophy, raised creatine k inase, sensorimotor peripheral neuropathy, and oxidative phosphorylation de fect on muscle biopsy.