Giant axonal neuropathy locus refinement to a < 590 kb critical interval

Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerati ve disorder, characterised clinically by the development of chronic distal polyneuropathy during childhood, mental retardation, kinky or curly hair, s keletal abnormalities and, ultrastructurally, by axons in the central and p eripheral nervous systems distended by masses of tightly woven neurofilamen ts. We recently localised the CAN locus in 16q24.1 to a 5-cM interval betwe en the D16S507 and D16S511 markers by homozygosity mapping in three consang uineous Tunisian families. We have now established a contig-based physical map of the region comprising YACs and BACs where we have placed four genes, ten ESTs, three STSs and two additional microsatellite markers, and where we have identified six new SSCP polymorphisms and six new microsatellite ma rkers. Using these markers, we have refined the position of our previous fl anking recombinants. We also identified a shared haplotype between two Tuni sian families and a small region of homozygosity in a Turkish family with d istant consanguinity, both suggesting the occurrence of historic recombinat ions and supporting the conclusions based on the phase-known recombinations . Taken together, these results allow us to establish a transcription map o f the region, and to narrow down the GAN position to a < 590 kb critical in terval, an important step toward the identification of the defective gene.