AUTOSOMAL-DOMINANT SPASTIC PARAPLEGIA LINKED TO CHROMOSOME 2P - CLINICAL AND GENETIC-STUDIES OF A LARGE JAPANESE PEDIGREE

Autosomal dominant spastic paraplegia (ADSP) is a genetically heteroge nous disorder. To date, 3 loci of ADSP have been identified on chromos ome 2p, 14q, and 15q, but specific gene mutations remain unknown. To d etermine the genetic background of ADSP in the Japanese, we studied a large 3-generation pedigree, clinically and genetically. Of the 36 ind ividuals clinically examined, 15 were affected. The main feature in th e affected individuals was a slowly progressive spastic paraplegia, as sociated with upper limb hyperreflexia (58%), reduction of vibration s ense (27%) and bladder disturbance (13%). Age at onset ranged from 13 to 50 years with a mean of 30.3+/-14.2 (SD). There were 6 parent-child pairs with anticipation and at least 3 others with 'anti-anticipation '. Linkage with 14q and 15q ADSP loci was excluded, and a highly signi ficant lod score was obtained only in the case of the 2p locus (Z(max) = 3.53 for D2S300/D2S352, at theta=0.00). Our study is the first to c onfirm the existence of 2p-linked ADSP in the Japanese. There is a sig nificant variety in age at onset and disease severity in these 2p-link ed families, but the implication for underlying ADSP mutation is not c lear. (C) 1997 Elsevier Science B.V.