MAPPING OF A 2ND LOCUS FOR LAMELLAR ICHTHYOSIS TO CHROMOSOME 2Q33-35

Lamellar ichthyosis (LI) is an inherited autosomal recessive disorder of cornification. It was recently demonstrated to result from deleteri ous mutations in the transglutaminase 1 (TGM1) gene. However, the dise ase was shown to be genetically heterogeneous, since some families wer e found to be unlinked to TGM1. Homozygosity mapping on three consangu inous families originating from Morocco shows (i) absence of linkage w ith TGM1 and other regions of the genome containing genes involved in cornification, and (ii) location of a second disease-causing gene on c hromosome 2q33-35. A maximum two-point lodscore of 7.60 was obtained w ith D2S157 for theta = 0. The analysis of re-combination events places the gene within a 7-8 cM interval. Additional consanguinous pedigrees were also demonstrated to be unlinked both to TGM1 and to 2q33-35, su ggesting the existence of at least a third disease-causing gene.