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Pediatr Diabetes. 2012 Feb;13(1):26-32. doi: 10.1111/j.1399-5448.2011.00827.x. Epub 2011 Nov 8.

Comprehensive molecular analysis of Japanese patients with pediatric-onset MODY-type diabetes mellitus.

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Department of Pediatric Endocrinology and Metabolism, Children's Medical Center, Osaka City General Hospital, 2-13-22 Miyakojima-Hondori, Miyakojima, Osaka 534-0021, Japan.

Erratum in

  • Pediatr Diabetes. 2013 May;14(3):230.



In Asians, mutations in the known maturity-onset diabetes of the young (MODY) genes have been identified in only <15% of patients. These results were obtained mostly through studies on adult patients.


To investigate the molecular basis of Japanese patients with pediatric-onset MODY-type diabetes.


Eighty Japanese patients with pediatric-onset MODY-type diabetes.


Mitochondrial 3243A>G mutation was first tested by the polymerase chain reaction restriction fragment length polymorphism analysis for maternally inherited families. Then, all coding exons and exon-intron boundaries of the HNF1A, HNF1B, GCK, and HNF4A genes were amplified from genomic DNA and directly sequenced. Multiplex ligation-dependent probe amplification analysis was also performed to detect whole-exon deletions.


After excluding one patient with a mitochondrial 3243A>G, mutations were identified in 38 (48.1%) patients; 18 had GCK mutations, 11 had HNF1A mutations, 3 had HNF4A mutations, and 6 had HNF1B mutations. In patients aged <8 yr, mutations were detected mostly in GCK at a higher frequency (63.6%). In patients >9 yr of age, mutations were identified less frequently (45.1%), with HNF1A mutations being the most frequent. A large fraction of mutation-negative patients showed elevated homeostasis model assessment (HOMA) insulin-resistance and normal HOMA-β indices. Most of the HNF1B mutations were large deletions, and, interestingly, renal cysts were undetectable in two patients with whole-gene deletion of HNF1B.


In Japanese patients with pediatric-onset MODY-type diabetes, mutations in known genes were identified at a much higher frequency than previously reported for adult Asians. A fraction of mutation-negative patients presented with insulin-resistance and normal insulin-secretory capacities resembling early-onset type 2 diabetes.

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