1.4 MB CANDIDATE GENE REGION FOR X-LINKED DYSKERATOSIS-CONGENITA DEFINED BY COMBINED HAPLOTYPE AND X-CHROMOSOME INACTIVATION ANALYSIS

Dyskeratosis congenita (DC) isa rare inherited disorder characterised by the early onset of reticulate skin pigmentation, nail dystrophy, an d mucosal leucoplakia. In over 80% of cases bone marrow failure develo ps and this is the main cause of early mortality. The DC1 gene respons ible for the X Linked form (MIM 305000) of dyskeratosis congenita has been mapped to Xq28. In order to narrow the candidate gene region, gen etic linkage analysis was performed in eight X linked pedigrees using a set of markers spanning Xq28. A maximum lod score of 5.31 with no re combinations was achieved with marker DXS1073. Two recombination event s were identified; one of these uses X chromosome inactivation pattern analysis to determine carrier status and haplotype analysis to fine m ap the recombination breakpoint. The fine mapping of these recombinati on events has enabled the candidate gene region for X Linked dyskerato sis congenita to be defined as the 1.4 Mb interval between Xq3274 and DXS1108.