- 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 language | English |
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| Article number | db190045 |
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| Pages (from-to) | 1528-1535 |
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| Number of pages | 8 |
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| Journal | Diabetes |
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| Volume | 68 |
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| Issue number | 7 |
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| Early online date | 8 Apr 2019 |
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| DOIs | |
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| Date | Accepted/In press - 4 Apr 2019 |
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| Date | E-pub ahead of print - 8 Apr 2019 |
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| Date | Published (current) - 1 Jul 2019 |
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| Additional links | |
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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.
© 2019 by the American Diabetes Association.
