Posterior column ataxia with retinitis pigmentosa (AXPC1) maps to chromosome lq31-q32

Objective: To establish a genetic linkage between highly polymorphic micros atellite loci and the disease locus responsible for an autosomal recessive neurodegenerative syndrome that causes posterior column ataxia and retiniti s pigmentosa. Background: The authors reported previously a genetic syndrom e that causes visual impairment, proprioceptive loss, sensory ataxia, and a reflexia in affected individuals from a large, inbred family belonging to a sectarian population that has been genetically semi-isolated from mainstre am society for several centuries. Methods: To find the disease locus respon sible for this condition, the authors performed a genome-wide search using genetic loci spaced at 10 to 20-cM intervals spanning human chromosomes (ch r) 1-22. Pairwise linkage analysis, multipoint linkage analysis, and haplot ype reconstruction were used to delineate the candidate region containing t he disease gene. Results: After testing 226 loci that covered the entire ge nome, the authors identified a maximum lod score of 8.94 at a recombination fraction of 0.00 for locus DIS2692. Additional analyses placed the disease gene, AXPC1, in an 8.3-cM interval flanked by markers DIS2692 and D1S414 o n chr 1q31-q32. Conclusions: This study suggests that a single genetic muta tion can cause selective degeneration of the posterior columns of the spina l cord and retina. Finding the gene responsible for this syndrome may incre ase our understanding of the molecular basis of diseases that affect sensor y neurons.