title: The onset of diabetes in three out of four sisters: a Japanese family with type 1 diabetes. A case report.
abstract: 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.
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Shiga, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Kishi
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kawabata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ugi
authors.forename: Tamaki
authors.initials: T
authors.lastname: Iwai
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshizaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Uzu
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Nishio
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegami
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maegawa
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000150:complications; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007564:Japan; D035781:Siblings
chemical_list: D001323:Autoantibodies; C024211:islet cell antibody