Mapping of a second 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 deleterious mutations in the transglutaminase 1 (TGM1) gene. However, the disease was shown to be genetically heterogeneous, since some families were found to be unlinked to TGM1. Homozygosity mapping on three consanguinous families originating from Morocco shows (i) absence of linkage with TGM1 and other regions of the genome containing genes involved in cornification, and (ii) location of a second disease-causing gene on chromosome 2q33-35. A maximum two-point lodscore of 7.60 was obtained with D2S157 for theta = 0. The analysis of recombination 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, suggesting the existence of at least a third disease-causing gene.