title: Posterior column ataxia and retinitis pigmentosa: a distinct clinical and genetic disorder.
abstract: Autosomal recessive posterior column ataxia and retinitis pigmentosa (PCARP) is a movement disorder that was genetically mapped to a disease locus (AXPC1) on chromosome 1q32-q31 in an inbred population of Dutch-German ancestry in the continental United States. We performed genetic linkage analysis and haplotype reconstruction on a different family from Spain with an identical phenotype to determine if the neurologic signs of an early-onset ataxia, retinitis pigmentosa, and a sensory neuropathy also mapped to the AXPC1 locus. The disease phenotype was linked in the candidate interval with a maximum lod score of 3.56 at a recombination fraction of 0.0 for locus D1S414. Haplotypes were discordant and suggested that the disease mutation arose independently from at least two populations. These results refine the classification of early-onset ataxia, abrogate a founder effect for this recessive disorder, and provide evidence that PCARP is a distinct, homogeneous, clinical, and genetic disorder.
authors.affiliation: Laboratory of Clinical Neurogenetics, Wadsworth Center, New York State Department of Health, Albany 12201-0509, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Higgins
authors.forename: K
authors.initials: K
authors.lastname: Kluetzman
authors.forename: J
authors.initials: J
authors.lastname: Berciano
authors.forename: O
authors.initials: O
authors.lastname: Combarros
authors.forename: J M
authors.initials: JM
authors.lastname: Loveless
mesh_terms: D002648:Child; D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D002874:Chromosome Mapping; D003241:Consanguinity; D005260:Female; D005808:Genes, Recessive / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D010375:Pedigree; D010641:Phenotype; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000235:genetics*; D013132:Spinocerebellar Degenerations / Q000175:diagnosis / Q000235:genetics*