A new locus for autosomal recessive spastic paraplegia associated with mental retardation and distal motor neuropathy, SPG14, maps to chromosome 3q27-q28

Abstract

Hereditary spastic paraplegias (HSPs), a group of neurodegenerative disorders that cause progressive spasticity of the lower limbs, are characterized by clinical and genetic heterogeneity. To date, three loci for autosomal recessive HSP have been mapped on chromosomes 8p, 16q, and 15q. After exclusion of linkage at these loci, we performed a genomewide search in a consanguineous Italian family with autosomal recessive HSP complicated by mild mental retardation and distal motor neuropathy. Using homozygosity mapping, we obtained positive LOD scores for markers on chromosome region 3q27-q28, with a maximum multipoint LOD score of 3.9 for marker D3S1601. Haplotype analysis allowed us to identify a homozygous region (4.5 cM), flanked by markers D3S1580 and D3S3669, that cosegregates with the disease. These data strongly support the presence, on chromosome 3q27-28, of a new locus for complicated recessive spastic paraplegia, which we have named "SPG14."

Figure 1

Pedigree of the family with ARHSP. Blackened and unblackened symbols represent affected and unaffected individuals, respectively. Genetic map is according to information from the Genetic Location Database. Haplotype analysis for the 3q27-q28 region showed a homozygous region cosegregating with the disease. Boxes represent the disease-bearing chromosome; blackened portions of the boxes, the regions of homozygosity carried only by affected individuals; arrows, recombination events. Bracketed haplotypes are deduced.