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Type 1 Diabetes Genetic Risk Score Discriminates Between Monogenic and Type 1 Diabetes in Children Diagnosed at the Age of <5 Years in the Iranian Population Publisher Pubmed



Yaghootkar H1 ; Abbasi F2 ; Ghaemi N3 ; Rabbani A2 ; Wakeling MN4 ; Eshraghi P3 ; Enayati S5 ; Vakili S6 ; Heidari S2 ; Patel K4 ; Sayarifard F2 ; Borhandayani S5 ; Mcdonald TJ4, 7 ; Ellard S4, 7 Show All Authors
Authors
  1. Yaghootkar H1
  2. Abbasi F2
  3. Ghaemi N3
  4. Rabbani A2
  5. Wakeling MN4
  6. Eshraghi P3
  7. Enayati S5
  8. Vakili S6
  9. Heidari S2
  10. Patel K4
  11. Sayarifard F2
  12. Borhandayani S5
  13. Mcdonald TJ4, 7
  14. Ellard S4, 7
  15. Hattersley AT4
  16. Amoli MM5
  17. Vakili R3, 6
  18. Colclough K8
Show Affiliations
Authors Affiliations
  1. 1. Genetics of Complex Traits, University of Exeter Medical School, Royal Devon & Exeter Hospital, Exeter, United Kingdom
  2. 2. Growth and Development Research Centre, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Paediatric Disease, Faulty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  4. 4. Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, United Kingdom
  5. 5. Metabolic Disorders Research Centre, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Medical Genetics Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran
  7. 7. Departments of Clinical Biochemistry, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom
  8. 8. Departments of Molecular Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom

Source: Diabetic Medicine Published:2019


Abstract

Aim: To examine the extent to which discriminatory testing using antibodies and Type 1 diabetes genetic risk score, validated in European populations, is applicable in a non-European population. Methods: We recruited 127 unrelated children with diabetes diagnosed between 9 months and 5 years from two centres in Iran. All children underwent targeted next-generation sequencing of 35 monogenic diabetes genes. We measured three islet autoantibodies (islet antigen 2, glutamic acid decarboxylase and zinc transporter 8) and generated a Type 1 diabetes genetic risk score in all children. Results: We identified six children with monogenic diabetes, including four novel mutations: homozygous mutations in WFS1 (n=3), SLC19A2 and SLC29A3, and a heterozygous mutation in GCK. All clinical features were similar in children with monogenic diabetes (n=6) and in the rest of the cohort (n=121). The Type 1 diabetes genetic risk score discriminated children with monogenic from Type 1 diabetes [area under the receiver-operating characteristic curve 0.90 (95% CI 0.83–0.97)]. All children with monogenic diabetes were autoantibody-negative. In children with no mutation, 59 were positive to glutamic acid decarboxylase, 39 to islet antigen 2 and 31 to zinc transporter 8. Measuring zinc transporter 8 increased the number of autoantibody-positive individuals by eight. Conclusions: The present study provides the first evidence that Type 1 diabetes genetic risk score can be used to distinguish monogenic from Type 1 diabetes in an Iranian population with a large number of consanguineous unions. This test can be used to identify children with a higher probability of having monogenic diabetes who could then undergo genetic testing. Identification of these individuals would reduce the cost of treatment and improve the management of their clinical course. © 2019 Diabetes UK
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