Diabetes Mellitus in a Japanese Girl with HDR Syndrome and GATA3 Mutation

Abstract. We report on a Japanese girl with HDR (hypoparathyroidism, sensorineural deafness, and renal dysplasia) syndrome who developed diabetes mellitus (DM) at three years of age (blood glucose 713 mg/dL, HbA1c 8.0%) in the absence of anti-glutamic acid decarboxylase autoantibodies. Mutation analysis revealed a de novo heterozygous two base pair deletion at exon 6 of the GATA3 gene (c.1200_1201delCA; p.H400fsX506). GATA3 expression was identified by PCR amplification for human pancreas cDNA, and mouse Gata3 was weekly but unequivocally expressed in pancreatic β cells. The results, in conjunction with the previous findings indicating the critical role of GATA3 in lymphocyte function, suggest that GATA3 haploinsufficiency may affect the function of β cells and/or lymphocytes, leading to the development of DM in relatively exceptional patients with high susceptibility to DM.