Trisomy 21 Is a Cause of Permanent Neonatal Diabetes That Is Autoimmune but Not HLA Associated

被引：24

作者：

Johnson, Matthew B. ^{[1
]}

De Franco, Elisa ^{[1
]}

Greeley, Siri Atma W. ^{[2
]}

Letourneau, Lisa R. ^{[2
]}

Gillespie, Kathleen M. ^{[3
]}

Wakeling, Matthew N. ^{[1
]}

Ellard, Sian ^{[1
]}

Flanagan, Sarah E. ^{[1
]}

Patel, Kashyap A. ^{[1
]}

Hattersley, Andrew T. ^{[1
]}

机构：

[1] Univ Exeter, Sch Med, Inst Biomed & Clin Sci, Exeter, Devon, England

[2] Univ Chicago, Sect Adult & Pediat Endocrinol Diabet & Metab, Kovler Diabet Ctr, Chicago, IL 60637 USA

[3] Univ Bristol, Bristol Med Sch, Bristol, Avon, England

来源：

DIABETES | 2019年 / 68卷 / 07期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; GENETIC RISK SCORE; DOWN-SYNDROME; EARLY-ONSET; TYPE-1; SUSCEPTIBILITY; MUTATIONS; AIRE; AUTOANTIBODIES; EXPRESSION;

D O I：

10.2337/db19-0045

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Identifying new causes of permanent neonatal diabetes (PNDM) (diagnosis <6 months) provides important insights into beta-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.

引用

页码：1528 / 1535

页数：8

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