Mapping Of A Novel Locus For Ichthyosis Vulgaris At 5p13.3-p12

Ichthyosis Vulgaris (IV) is one of the most common hereditary skin disorders, with a prevalence at 1 in 250-5300. In the Chinese population, the prevalence rate is about 0.23%. The onset of IV is usually within one year after birth. The patients manifest with white scaling on the extensor surfaces of the extremities and occasionally the trunk. Associated clinical features also include hyperlinearity of the palms and soles, atopy and heat intolerance or keratosis pilaris. Genetically, IV is inherited in autosomal dominant pattern, with genetic heterogeneity. At least two loci were mapped to 1q21 and 1q22 in the previous study. Mutations in filaggrin gene (FLG) were detected in IV patients, which is the only gene to be identified for IV.In our study, we collected a family with IV from Xupu in Hunan province. The family has 4 generations with 26 individuals. 23 individuals were analyzed, including 5 male and 9 female patients. The disease in this family is inherited as autosomal-dominant pattern. According to the reported study, FLG gene was first screened for mutation, no disease causative mutation was found. Genotyping and linkage analysis to STR markers at known chromosome 1 was further processed for family and the known loci for IV were excluded, suggesting a novel locus may be associated with the disease in this family. We then performed genome-wide scan and linkage analysis in the family. Maximal LOD scores 3.00 at D2S151 (θ=0), 2.05 at D4S1525 (θ=0.1) and 2.66 at D5S426 (0=0) were obtained respectively. Fine mapping was consequently carried out using the Marshfield markers around the three suspect loci. Linkage analysis and haplotype construction exclude chromosome 2 and 4. The haplotype was co-segeragated with the phenotype at chromosome 5, which finally localized a novel locus for IV to a 14.51cM region between d5sl470 and d5s2087 at 5pl3.3-pl2.According to the pathological change in IV, we searched for possible candidate genes between D5S1470 and D5S2087 by candidate approach. 9 candidate genes were firstly screened for mutation in this family. However, no mutation was identified to be associated with disease. Mutation analysis in non-coding region of these 9 genes and more candidate genes may help us to find out the molecular mechanisms of the disease in this family.