Genome-wide scan identifies a susceptibility locus for familial primary cutaneous amyloidosis on chromosome 5p13.1-q11.2

Background: Primary cutaneous amyloidosis (PCA) is a relatively common skin disorder in South America and Southeast Asia. Most cases of PCA are sporadic but familial aggregation has been reported from South America and Taiwan. The different susceptibility among ethnic groups suggests that genetic factors may play an important role in its pathogenesis. Objectives: We aimed to perform a genome-wide scan by linkage analysis across 15 families with familial primary cutaneous amyloidosis (FPCA) to map the disease gene(s) for FPCA. Patients and methods: A total of 15 FPCA families including 50 individuals affected with PCA were recruited. Throughout the 22 autosomes, 369 polymorphic microsatellite markers were used initially. Regions showing a LOD score > 1 identified in the initial scan were further analysed with additional markers. Two-point and multipoint linkage analysis were performed by using the LINKAGE program. Nonparametric linkage (NPL) analysis and reconstruction of haplotypes were performed with the GENEHUNTER program. Results: A maximum two-point LOD score of 4.76 for the marker D5S1490 (θ = 0.10, α = 0.60) and a multipoint LOD score of 4.50 between D5S822 and D5S623 (α = 0.60) were obtained under the assumption of heterogeneity. A peak NPL score of 5.23 (P value = 0.000007) was found from D5S1490 to D5S2076. Further analysis focusing on two major families identifies a common haplotype shared by all affected individuals between D5S1490 and D5S623. To our knowledge, this is the first report of genome-wide analysis of a large number of FPCA pedigrees. Conclusions: Our study provides evidence for significant linkage to chromosome 5p13.1-q11.2 in a subset of FPCA families.