dc.contributor.author | Yaghootkar, H | |
dc.contributor.author | Abbasi, F | |
dc.contributor.author | Ghaemi, N | |
dc.contributor.author | Rabbani, A | |
dc.contributor.author | Wakeling, MN | |
dc.contributor.author | Eshraghi, P | |
dc.contributor.author | Enayati, S | |
dc.contributor.author | Vakili, S | |
dc.contributor.author | Heidari, S | |
dc.contributor.author | Patel, K | |
dc.contributor.author | Sayarifard, F | |
dc.contributor.author | Borhan-Dayani, S | |
dc.contributor.author | McDonald, TJ | |
dc.contributor.author | Ellard, S | |
dc.contributor.author | Hattersley, AT | |
dc.contributor.author | Amoli, MM | |
dc.contributor.author | Vakili, R | |
dc.contributor.author | Colclough, K | |
dc.date.accessioned | 2019-10-28T15:48:45Z | |
dc.date.issued | 2019-07-05 | |
dc.description.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. | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | Diabetes UK | en_GB |
dc.identifier.citation | Vol. 36 (12), pp. 1694-1702 | en_GB |
dc.identifier.doi | 10.1111/dme.14071 | |
dc.identifier.grantnumber | 108101/Z/15/Z | en_GB |
dc.identifier.grantnumber | 17/0005594 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/39354 | |
dc.language.iso | en | en_GB |
dc.publisher | Wiley for Diabetes UK | en_GB |
dc.rights | © 2019 Diabetes UK | en_GB |
dc.rights | © 2019 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | |
dc.title | 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 | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-10-28T15:48:45Z | |
dc.identifier.issn | 0742-3071 | |
dc.description | This is the final version. Available on open access from Wiley via the DOI in this record | en_GB |
dc.identifier.journal | Diabetic Medicine | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2019-07-03 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2019-07-05 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-10-28T15:46:06Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2020-01-20T12:47:00Z | |
refterms.panel | A | en_GB |