Diabetes mellitus in a Japanese girl with HDR syndrome and GATA3 mutation.
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, HbA(1c) 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 beta cells. The results, in conjunction with the previous findings indicating the critical role of GATA3 in lymphocyte function, GATA3 haploinsufficiency may affect the function of beta cells and/or lymphocytes, leading to the development of DM in relatively exceptional patients with high susceptibility to DM.
Muroya
Koji
K
Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, 2-10-1 Ohkura, Setagaya, Tokyo, Japan.
Mochizuki
Takahiro
T
Fukami
Maki
M
Iso
Manami
M
Fujita
Keinosuke
K
Itakura
Mitsuo
M
Ogata
Tsutomu
T
D000818:Animals; D044466:Asian People; D002648:Child; D002675:Child, Preschool; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics*; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007011:Hypoparathyroidism / Q000235:genetics*; D017403:In Situ Hybridization; D007223:Infant; D052177:Kidney Diseases, Cystic / Q000235:genetics*; D051379:Mice; D017384:Sequence Deletion; D013577:Syndrome
D050990:GATA3 Transcription Factor