Autosomal dominant spastic paraplegia linked to chromosome 2p: clinical and genetic studies of a large Japanese pedigree

J Neurol Sci. 1997 Oct 3;151(1):65-70. doi: 10.1016/s0022-510x(97)00107-x.


Autosomal dominant spastic paraplegia (ADSP) is a genetically heterogenous disorder. To date, 3 loci of ADSP have been identified on chromosome 2p, 14q, and 15q, but specific gene mutations remain unknown. To determine the genetic background of ADSP in the Japanese, we studied a large 3-generation pedigree, clinically and genetically. Of the 36 individuals clinically examined, 15 were affected. The main feature in the affected individuals was a slowly progressive spastic paraplegia, associated with upper limb hyperreflexia (58%), reduction of vibration sense (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 significant lod score was obtained only in the case of the 2p locus (Zmax = 3.53 for D2S400/D2S352, at theta = 0.00). Our study is the first to confirm the existence of 2p-linked ADSP in the Japanese. There is a significant variety in age at onset and disease severity in these 2p-linked families, but the implication for underlying ADSP mutation is not clear.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Chromosomes, Human, Pair 2*
  • Genes, Dominant*
  • Genetic Linkage
  • Genotype
  • Humans
  • Japan
  • Lod Score
  • Middle Aged
  • Pedigree
  • Spastic Paraplegia, Hereditary / genetics*