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  • Oral presentation
  • Open Access

Molecular basis of transient neonatal diabetes mellitus in Japan: frequent KATP-TNDM and identification of a patient with a monoallelic INS mutation

  • 1, 2, 3,
  • 1,
  • 1,
  • 1,
  • 1,
  • 1 and
  • 2, 3
International Journal of Pediatric Endocrinology20152015 (Suppl 1) :O32

https://doi.org/10.1186/1687-9856-2015-S1-O32

  • Published:

Keywords

  • Molecular Basis
  • Japanese Patient
  • KATP Channel
  • Channel Gene
  • Promoter Mutation

Background

It has been reported that the most common (~70%) form of transient neonatal diabetes mellitus (TNDM) is 6q24-related TNDM, followed by TNDM caused by activating mutations in the KATP channel genes (KCNJ11 and ABCC8, KATP-TNDM) which accounts for approximately 30% of TNDM. Recessive promoter mutations in the insulin (INS) gene also have been reported as rare causes of TNDM.

Aims

To elucidate the molecular basis of TNDM in Japan.

Methods

Nineteen Japanese patients with TNDM were analysed by methylation specific PCR of the differentially methylated region at chromosome 6q24 and by PCR amplification and direct sequencing of all exons and exon-intron boundaries of the KCNJ11, ABCC8, and INS genes.

Results

6q24 abnormalities were identified in 7 (paternal duplication in 4, paternal uniparental disomy or epimutation in 3), mutations of ABCC8 (R1380C, R216C, V607M) in 3, KCNJ11 (E227K, R50Q, C42R) in 3, and INS (Q62X) in 1.

Conclusion

As compared with previous reports, the frequency of KATP channel mutations were higher in this Japanese cohort. In addition, this is the first report of a monoallelic, coding sequence mutation in the INS gene (Q62X) responsible for TNDM.

Authors’ Affiliations

(1)
Department of Pediatric Endocrinology and Metabolism, Children's Medical Center, Osaka City General Hospital, Japan
(2)
Department of Genetic Medicine, Osaka City General Hospital, Japan
(3)
Clinical Research Center, Osaka City General Hospital, Japan

Copyright

© Yorifuji et al; licensee BioMed Central Ltd. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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