Abstract
Diabetes mellitus is a multifactorial disease caused by a complex interaction of environmental and genetic factors. Some diabetes mellitus cases, however, are caused by a limited number of mutant genes. Chromosome 13q deletion syndrome, an extremely rare genetic disorder, is caused by structural and functional monosomy of the 13q chromosomal region. We report the case of a 38-year-old Japanese man with Chr13q deletion (a mosaic pattern with heterozygous ring Chr13q) who developed diabetes mellitus. Early-onset diabetes mellitus developed in this patient because of insulin resistance and a lack of adequate insulin secretion. Microarray analysis identified a 4.8-Mb deletion of distal Chr13q, leading to a copy number loss of 40 genes. Among those genes, the insulin receptor substrate 2 gene (IRS2) was the most likely causative candidate for the development of diabetes mellitus in this patient, based on the model of IRS2 knockout mice, which have abnormal glucose and insulin homeostasis closely resembling the human diabetes phenotype. These data provide important information regarding the contribution of a microdeletion of Chr13q, including in IRS2, to the pathogenesis of diabetes mellitus in humans.