De Franco E, Flannagan SE, Houghton JA, Lango Allen H, Mackay DJ, et al. The effect of early, comprehensive genomic testing on clinical care in neonatal diabetes: an international cohort study. Lancet 2015;386:957–63.PubMedCrossrefWeb of ScienceGoogle Scholar
Johansson BB, Irgens HU, Molnes J, Sztromwasser P, Aukrust I, et al. Targeted next-generation sequencing reveals MODY in up to 6.5% of antibody-negative diabetes cases listed in the Norwegian Childhood Diabetes Registry. Diabetologia 2017;60:625–35.Web of SciencePubMedCrossrefGoogle Scholar
Delvecchio M, Mozzillo E, Salzano G, Iafusco D, Frontino G, et al. Monogenic diabetes accounts for 6.3% of cases referred to 15 Italian pediatric diabetes centers during 2007 to 2012. J Clin Endocrinol Metab 2017;102:1826–34.CrossrefPubMedWeb of ScienceGoogle Scholar
Shields BM, Shepherd M, Hudson M, McDonald TJ, Colclough K, et al. Population-based assessment of a biomarker-based screening pathway to aid diagnosis of monogenic diabetes in young-onset patients. Diabetes Care 2017;40:1017–25.CrossrefPubMedWeb of ScienceGoogle Scholar
Bennett CL, Christie J, Ramsdell F, Brunkow ME, Ferguson PJ, et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat Genet 2001;27:20–1.CrossrefPubMedGoogle Scholar
Sediva H, Dusatkova P, Kanderova V, Obermannova B, Kayserova J, et al. Short stature in a boy with multiple early-onset autoimmune conditions due to activating mutation: could intracellular growth hormone signalling be compromised? Horm Res Paediatr 2017;88:160–6.Web of ScienceCrossrefGoogle Scholar
Caudy AA, Reddy ST, Chatila T, Atkinson JP, Verbsky JW. CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome, and defective IL-10 expression from CD4 lymphocytes. J Allergy Clin Immunol 2007;119:482–7.CrossrefPubMedWeb of ScienceGoogle Scholar
Flanagan SE, Haapaniemi E, Russell MA, Caswell R, Allen HL, et al. Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease. Nat Genet 2014;46:812–4.CrossrefPubMedWeb of ScienceGoogle Scholar
Kuehn HS, Ouyang W, Lo B, Deenick EK, Niemela JE, et al. Immune dysregulation in human subjects with heterozygous germline mutations in CTLA4. Science 2014;345:1623–7.CrossrefPubMedWeb of ScienceGoogle Scholar
Johnson MB, De Franco E, Lango Allen H, Al Senani A, Elbarbary N, et al. Recessively inherited LRBA mutations cause autoimmunity presenting as neonatal diabetes. Diabetes 2017;66:2316–22.PubMedCrossrefWeb of ScienceGoogle Scholar
Toubiana J, Okada S, Hiller J, Oleastro M, Lagos Gomez M, et al. Heterozygous STAT1 gain-of-function mutations underlie an unexpectedly broad clinical phenotype. Blood 2016;127:3154–64.PubMedCrossrefWeb of ScienceGoogle Scholar
Hughes JW, Riddlesworth TD, DiMeglio LA, Miller KM, Rickels MR, et al. Autoimmune diseases in children and adults with type 1 diabetes from the T1D Exchange clinic registry. J Clin Endocrinol Metab 2016;101:4931–7.Web of SciencePubMedCrossrefGoogle Scholar
Lo B, Zhang K, Lu W, Zheng L, Zhang Q, et al. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science 2015;349:436–40.CrossrefWeb of SciencePubMedGoogle Scholar
Horino S, Sasahara Y, Sato M, Niizuma H, Kumaki S, et al. Selective expansion of donor-derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome. Pediatr Transplant 2014;18:25–30.Web of ScienceCrossrefGoogle Scholar
Huopio H, Miettinen PJ, Ilonen J, Nykänen P, Veijola R, et al. Clinical, genetic, and biochemical characteristics of early-onset diabetes in the Finnish population. J Clin Endocrinol Metab 2016;101:3018–26.CrossrefPubMedWeb of ScienceGoogle Scholar
Johnson MB, Patel KA, De Franco E, Houghton JA, McDonald TJ, et al. A type 1 diabetes genetic risk score can discriminate monogenic autoimmunity with diabetes from early-onset clustering of polygenic autoimmunity with diabetes. Diabetologia 2018;61:862–9.CrossrefWeb of SciencePubMedGoogle Scholar
Schweiger DS, Mendez A, Jamnik SK, Bratanic N, Bratina N, et al. High-risk genotypes HLA-DR3-DQ2/DR3-DQ2 and DR3-DQ2/DR4-DQ8 in co-occurrence of type 1 diabetes and celiac disease. Autoimmunity 2016;49:240–7.CrossrefWeb of SciencePubMedGoogle Scholar
Oram RA, Patel K, Hill A, Shields B, McDonald TJ, et al. A type 1 diabetes genetic risk score can aid discrimination between type 1 and type 2 diabetes in young adults. Diabetes Care 2016;39:337–44.CrossrefPubMedWeb of ScienceGoogle Scholar
Patel KA, Oram RA, Flanagan SE, De Franco E, Colclough K, et al. Type 1 diabetes genetic risk score: a novel tool to discriminate monogenic and type 1 diabetes. Diabetes 2016;65:2094–9.CrossrefWeb of ScienceGoogle Scholar
Petruzelkova L, Ananieva-Jordanova R, Vcelakova J, Vesely Z, Stechova K, et al. The dynamic changes of zinc transporter 8 autoantibodies in Czech children from the onset of Type 1 diabetes mellitus. Diabet Med 2014;31:165–71.CrossrefPubMedGoogle Scholar
Husby S, Koletzko S, Korponay-Szabó IR, Mearin ML, Phillips A, et al. European society for pediatric gastroenterology, hepatology, and nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr 2012;54:136–60.CrossrefWeb of ScienceGoogle Scholar
Andrews S. FastQC a quality control tool for high throughput sequence data. https://www.bioinformatics.babraham.ac.uk/projects/fastqc/. Accessed: 25 Aug 2017.
Pruhova S, Dusatkova P, Sumnik Z, Kolouskova S, Pedersen O, et al. Glucokinase diabetes in 103 families from a country-based study in the Czech Republic: geographically restricted distribution of two prevalent GCK mutations. Pediatr Diabetes 2010;11:529–35.CrossrefWeb of SciencePubMedGoogle Scholar
Romanos J, Wijmenga C. Comment on: Barker et al. (2008) Two single nucleotide polymorphisms identify the highest-risk diabetes HLA genotype: Diabetes 57:3152-3155, 2008. Diabetes 2009;58:e1.CrossrefGoogle Scholar
Parackova Z, Kayserova J, Danova K, Sismova K, Dudkova E, et al. T regulatory lymphocytes in type 1 diabetes: impaired CD25 expression and IL-2 induced STAT5 phosphorylation in paediatric patients. Autoimmunity 2016;49:523–31.CrossrefGoogle Scholar
Schwab C, Gabrysch A, Olbrich P, Patiño V, Warnatz K, et al. Phenotype, penetrance, and treatment of 133 CTLA-4-insufficient individuals. J Allergy Clin Immunol 2018;142:1932–46.CrossrefGoogle Scholar
About the article
Published Online: 2019-09-04
Published in Print: 2019-10-25
Funding Source: Ministry of Health of the Czech Republic
Award identifier / Grant number: NV18-01-007
The study was funded by the Grant Agency of Charles University in Prague (no. GAUK 216217), the Ministry of Health of the Czech Republic (funder Id: http://dx.doi.org/10.13039/501100003243) (no. NV18-01-0078) and the Welcome Trust Senior Investigator Award (no. 098395/Z/12/Z).
Author contributions: VS analysed the data and wrote the manuscript; SP designed the study and reviewed/edited the manuscript; LE analysed the data and wrote the manuscript; MBJ researched data and reviewed/edited the manuscript; ATH reviewed/edited the manuscript; PD designed the study and reviewed/edited the manuscript; BO investigated the patients; LP investigated the patients and reviewed/edited the manuscript; SK investigated the patients and reviewed/edited the manuscript; MaS investigated the patients; JL reviewed/edited the manuscript; ZS reviewed/edited the manuscript; EF analysed the data and reviewed/edited the manuscript; MiS analysed the data and reviewed/edited the manuscript. All authors made substantial contributions to the acquisition and interpretation of data, revised the manuscript critically for important intellectual content and approved the final version to be published. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.