Abstract:
:Identifying new causes of permanent neonatal diabetes (PNDM) (diagnosis <6 months) provides important insights into β-cell biology. Patients with Down syndrome (DS) resulting from trisomy 21 are four times more likely to have childhood diabetes with an intermediate HLA association. It is not known whether DS can cause PNDM. We found that trisomy 21 was seven times more likely in our PNDM cohort than in the population (13 of 1,522 = 85 of 10,000 observed vs. 12.6 of 10,000 expected) and none of the 13 DS-PNDM patients had a mutation in the known PNDM genes that explained 82.9% of non-DS PNDM. Islet autoantibodies were present in 4 of 9 DS-PNDM patients, but DS-PNDM was not associated with polygenic susceptibility to type 1 diabetes (T1D). 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 T1D that is HLA associated and diabetes caused by trisomy 21 that is not HLA associated.
journal_name
Diabetesjournal_title
Diabetesauthors
Johnson MB,De Franco E,Greeley SAW,Letourneau LR,Gillespie KM,International DS-PNDM Consortium.,Wakeling MN,Ellard S,Flanagan SE,Patel KA,Hattersley ATdoi
10.2337/db19-0045subject
Has Abstractpub_date
2019-07-01 00:00:00pages
1528-1535issue
7eissn
0012-1797issn
1939-327Xpii
db19-0045journal_volume
68pub_type
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