The onset of diabetes in three out of four sisters: a Japanese family with type 1 diabetes. A case report.

Type 1A diabetes is an autoimmune disease characterized by the destruction of insulin-producing beta-cells in the pancreas. The HLA-DR and -DQ genes are well established as being associated with increased risk for type 1 diabetes. Moreover, polymorphisms in CTLA4 have been reported to be associated with susceptibility to type 1 diabetes and autoimmune thyroid disease (AITD). In both Caucasian and Japanese populations, the lifetime risk in siblings of type 1 diabetic probands is much higher than that in general populations. However, in Japan, where the prevalence of type 1 diabetes is less than one-tenth that of most Caucasian populations, it is rare for type 1 diabetes to develop in three or more siblings within a family. Here, we report a Japanese family in which type 1 diabetes occurred in three siblings amongst four sisters. Three probands of type 1 diabetes had the same combination of HLA haplotypes, DRB1(*)0405-DQB1(*)0401/ DRB1(*)0802-DQB1(*)0302, which occurs significantly more often in type 1 diabetes patients than in control subjects in the Japanese population. With respect to the rs3087243 (+6230G>A) polymorphism of CTLA4, the first sister had type 1 diabetes and AITD and had the GG genotype, whereas the second and third sisters, who had type 1 diabetes without AITD, had the AG genotype. This is the first report of a family in which type 1A diabetes developed in three siblings. We performed genetic analysis of HLA-DR, -DQ, and CTLA4 in all family members. Even in a country where the prevalence of type 1 diabetes is low, diabetic proband siblings should be monitored for the onset of type 1 diabetes.