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

Objective: To establish a genetic linkage between highly polymorphic microsatellite loci and the disease locus responsible for an autosomal recessive neurodegenerative syndrome that causes posterior column ataxia and retinitis pigmentosa. Background: The authors reported previously a genetic syndrome that causes visual impairment, proprioceptive loss, sensory ataxia, and areflexia in affected individuals from a large, inbred family belonging to a sectarian population that has been genetically semi-isolated from mainstream society for several centuries. Methods: To find the disease locus responsible for this condition, the authors performed a genome-wide search using genetic loci spaced at 10 to 20-cM intervals spanning human chromosomes (chr) 1-22. Pairwise linkage analysis, multipoint linkage analysis, and haplotype reconstruction were used to delineate the candidate region containing the disease gene. Results: After testing 226 loci that covered the entire genome, 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 on chr 1q31-q32. Conclusions: This study suggests that a single genetic mutation can cause selective degeneration of the posterior columns of the spinal cord and retina. Finding the gene responsible for this syndrome may increase our understanding of the molecular basis of diseases that affect sensory neurons.