Published in:
01-12-2012 | Original article
Whole gene deletion mutation of HNF1B and exonic aberration mutations of GCK and HNF1B in patients with MODY in Japan
Published in: Diabetology International | Issue 4/2012
Login to get accessAbstract
Aims
Recent reports indicate that genomic rearrangements are novel causative mutations for maturity onset diabetes of the young (MODY). The aim of this study was to investigate genomic rearrangements in Japanese patients with MODY.
Methods
Subjects diagnosed with diabetes before the age of 30 years and clinically suspected of having MODY but without identified causative mutations were included in the study (n = 223). Multiplex ligation-dependent probe amplification (MLPA) assays were performed to detect genomic rearrangements in HNF4A, GCK, HNF1A, and HNF1B. Array comparative genomic hybridization (aCGH) was performed to confirm the presence and extent of complete gene deletion or duplications. To examine variation in exon copy number, a custom MODY-CGH microarray using the web-based Agilent eArray database was performed.
Results
Four subjects with a hemizygous deletion mutation at 17q12, including HNF1B and spanning 1.4 Mb, were identified. The clinical features of these patients corresponded to those of MODY5 patients. In addition, one case each with an exon copy number variation of GCK7 and HNF1B3 were identified by MLPA and confirmed by array CGH.
Conclusions
We identified four Japanese MODY cases with a genomic rearrangement in MODY5. Our data indicate that when diagnosing MODY5, the typical phenotype is more important than the family history because the cases detected occurred de novo. Moreover, we report the first Japanese cases with exonic copy number variation of the genes for MODY2 and 5.