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Trisomy 21 is a Cause of Permanent Neonatal Diabetes that is Autoimmune but not HLA Associated

Research output: Contribution to journalArticle

  • Matthew B. Johnson
  • Elisa De Franco
  • Siri Atma W. Greeley
  • Lisa R. Letourneau
  • Kathleen M. Gillespie
  • Matthew N. Wakeling
  • Sian Ellard
  • Sarah E. Flanagan
  • Kashyap A. Patel
  • Andrew T. Hattersley
Original languageEnglish
Article numberdb190045
Pages (from-to)1528-1535
Number of pages8
Issue number7
Early online date8 Apr 2019
DateAccepted/In press - 4 Apr 2019
DateE-pub ahead of print - 8 Apr 2019
DatePublished (current) - 1 Jul 2019


Identifying new causes of permanent neonatal diabetes (diagnosis <6 months; PNDM) provides important insights into β-cell biology. Patients with Down syndrome (DS) resulting from trisomy 21 are 4 times more likely to have childhood diabetes with an intermediate HLA association. It is not known if DS can cause PNDM. We found trisomy 21 was 7 times more likely in our PNDM cohort than in the population (13/1522 = 85/10,000 observed vs. 12.6/10,000 expected) and none of the 13 DS-PNDM cases had a mutation in the known PNDM genes which explained 82.9% of non-DS PNDM. Islet autoantibodies were present in 4/9 DS-PNDM patients but DS-PNDM was not associated with polygenic susceptibility to type 1 diabetes. We conclude that trisomy 21 is a cause of autoimmune PNDM that is not HLA associated. We propose that autoimmune diabetes in DS is heterogeneous and includes coincidental type 1 diabetes that is HLA associated and diabetes caused by trisomy 21 that is not HLA associated.

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© 2019 by the American Diabetes Association.

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    Rights statement: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via the American Diabetes Association at . Please refer to any applicable terms of use of the publisher.

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