FAMILIAL SPASTIC PARAPARESIS - EVALUATION OF LOCUS HETEROGENEITY, ANTICIPATION, AND HAPLOTYPE MAPPING OF THE SPG4 LOCUS ON THE SHORT ARM OFCHROMOSOME-2

Familial spastic paraparesis (SPC;) is a clinically and genetically he terogeneous group of disorders. At least three loci have been implicat ed in autosomal dominant pure SPG and mutations in either of two loci may cause the X-linked form. Although the penetrance is high for all f orms by age 60, there is wide variation in clinical characteristics, i ncluding age of onset. Two-point and multipoint linkage analyses in ni ne families provided supportive evidence that the most common form of SPG is linked to chromosome 2 (SPG4). Haplotype analysis localized the critical region to a 6 cM interval between D2S392 and D2S367. By hapl otype analysis, the disease in at least one family does not appear to be linked to any of the presently known SPG loci, suggesting that ther e is at least one additional SPG gene. Evaluation of ages of onset in II families gave suggestive evidence for anticipation with mean age of onset in parents (41.3 years) being older than mean age of onset in c hildren (26.9 years; P < 0.005). (C) 1997 Wiley-Liss, Inc.