Locus heterogeneity, anticipation and reduction of the chromosome 2p minimal candidate region in autosomal dominant familial spastic paraplegia

• Published in: Neurogenetics Vol. 1; no. 2; pp. 95 - 102
• Main Authors: Scott, W K, Gaskell, P C, Lennon, F, Wolpert, C M, Menold, M M, Aylsworth, A S, Warner, C, Farrell, C D, Boustany, R M, Albright, S G, Boyd, E, Kingston, H M, Cumming, W J, Vance, J M, Pericak-Vance, M A
• Format: Journal Article
• Language: English
• Published: United States Springer Nature B.V 01.11.1997
• Subjects: Adolescent; Adult; Age of Onset; Aged; Child; Child, Preschool; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 14 - genetics; Chromosomes, Human, Pair 2 - genetics; DNA - genetics; Family Health; Female; Genes, Dominant; Genetic Heterogeneity; Genetic Linkage; Genetics; Genotype; Humans; Infant; Lod Score; Male; Medical research; Microsatellite Repeats; Middle Aged; Paraplegia - genetics; Pedigree
• ISSN: 1364-6745; 1364-6753
• DOI: 10.1007/s100480050014

We examined 11 Caucasian pedigrees with autosomal dominant 'uncomplicated' familial spastic paraplegia (SPG) for linkage to the previously identified loci on chromosomes 2p, 14q and 15q. Chromosome 15q was excluded for all families. Five families showed evidence for linkage to chromosome 2p, one to chromosome 14q, and five families remained indeterminate. Homogeneity analysis of combined chromosome 2p and 14q data gave no evidence for a fourth as yet unidentified SPG locus. Recombination events reduced the chromosome 2p minimum candidate region (MCR) to a 3 cM interval between D2S352 and D2S367 and supported the previously reported 7 cM MCR for chromosome 14q. Age of onset (AO) was highly variable, indicating that subtypes of SPG are more appropriately defined on a genetic basis than by AO. Comparison of AO in parent-child pairs was suggestive of anticipation, with a median difference of 9.0 years (p<0.0001).