Molecular genetics of familial spastic paraplegia

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The hereditary spastic paraplegia (HSP) is a group of rare disorders that are characterized by great clinical and genetic heterogeneity. To date, nine loci for autosomal dominant HSP, three loci for X-linked HSP, and four loci for autosomal recessive HSP have been characterized. We have clinically characterized 13 Japanese autosomal recessive HSP families and performed genetic linkage analyzes. All the 13 families were classified as the "complicated" forms, which manifested with mental impairment and thin corpus callosum (TCC). Linkage to the 8p12-q13 and 16qter loci was excluded, while ten of the 13 families showed marker data consistent with linkage to 15q13-15. The multipoint LOD score of the 10 families linked to chromosome 15 was above 9.00 in the 3 cM segment flanked by D15S994 and D15S659, with a maximum multipoint LOD score of 9.68 at a position 1.2 cM telomeric from D15S994 to D15S659. We have shown that ARHSP with TCC, a subtype of recessive spastic paraplegia maps to chromosome 15q13-15. We did not detect any linkage disequilibrium between ARHSP with TCC and the marker loci used in our study. Since the markers were located at 0.5 cM intervals in the study, use of more densely placed markers will be required for further investigation on the linkage disequilibrium.