Systematic genetic testing for recessively inherited monogenic diabetes: a cross-sectional study in paediatric diabetes clinics

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dc.authoridTeoman Akçay / 0000-0002-8252-7089
dc.authorscopusidTeoman Akçay / 23968688000
dc.authorwosidTeoman Akçay / AFG-8460-2022
dc.contributor.authorPatel, Kashyap A.
dc.contributor.authorOzbek, Mehmet N.
dc.contributor.authorYildiz, Melek
dc.contributor.authorGuran, Tulay
dc.contributor.authorKocyigit, Cemil
dc.contributor.authorAcar, Sezer
dc.contributor.authorSiklar, Zeynep
dc.contributor.authorAkçay, Teoman
dc.date.accessioned2021-11-02T08:39:07Z
dc.date.available2021-11-02T08:39:07Z
dc.date.issued2021en_US
dc.departmentİstinye Üniversitesi, Hastaneen_US
dc.description.abstractAims/hypothesis Current clinical guidelines for childhood-onset monogenic diabetes outside infancy are mainly focused on identifying and testing for dominantly inherited, predominantly MODY genes. There are no systematic studies of the recessively inherited causes of monogenic diabetes that are likely to be more common in populations with high rates of consanguinity. We aimed to determine the contribution of recessive causes of monogenic diabetes in paediatric diabetes clinics and to identify clinical criteria by which to select individuals for recessive monogenic diabetes testing. Methods We conducted a cross-sectional study of 1093 children from seven paediatric diabetes clinics across Turkey (a population with high rates of consanguinity). We undertook genetic testing of 50 known dominant and recessive causes of monogenic diabetes for 236 children at low risk of type 1 diabetes. As a comparison, we used monogenic diabetes cases from UK paediatric diabetes clinics (a population with low rates of consanguinity). Results Thirty-four children in the Turkish cohort had monogenic diabetes, equating to a minimal prevalence of 3.1%, similar to that in the UK cohort (p = 0.40). Forty-one per cent (14/34) had autosomal recessive causes in contrast to 1.6% (2/122) in the UK monogenic diabetes cohort (p < 0.0001). All conventional criteria for identifying monogenic diabetes (parental diabetes, not requiring insulin treatment, HbA(1c) <= 58 mmol/mol [<= 7.5%] and a composite clinical probability of MODY >10%) assisted the identification of the dominant (all p <= 0.0003) but not recessive cases (all p >= 0.2) in Turkey. The presence of certain non-autoimmune extra-pancreatic features greatly assisted the identification of recessive (p < 0.0001, OR 66.9) but not dominant cases. Conclusions/interpretation Recessively inherited mutations are a common cause of monogenic diabetes in populations with high rates of consanguinity. Present MODY-focused genetic testing strategies do not identify affected individuals. To detect all cases of monogenic paediatric diabetes, it is crucial that recessive genes are included in genetic panels and that children are selected for testing if they have certain non-autoimmune extra-pancreatic features in addition to current criteria.en_US
dc.identifier.citationPatel, K. A., Ozbek, M. N., Yildiz, M., Guran, T., Kocyigit, C., Acar, S., ... & Hattersley, A. T. (2021). Systematic genetic testing for recessively inherited monogenic diabetes: a cross-sectional study in paediatric diabetes clinics. Diabetologia, 1-7.en_US
dc.identifier.doi10.1007/s00125-021-05597-yen_US
dc.identifier.issn0012-186Xen_US
dc.identifier.issn1432-0428en_US
dc.identifier.pmid34686905en_US
dc.identifier.scopus2-s2.0-85117689028en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1007/s00125-021-05597-y
dc.identifier.urihttps://hdl.handle.net/20.500.12713/2197
dc.identifier.wosWOS:000710082900001en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorAkçay, Teoman
dc.language.isoenen_US
dc.publisherSPRINGERen_US
dc.relation.ispartofDIABETOLOGIAen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectDiabetes Syndromeen_US
dc.subjectMODYen_US
dc.subjectMonogenic Diabetesen_US
dc.subjectRecessive Monogenic Diabetesen_US
dc.subjectSyndromic Diabetesen_US
dc.subjectType 1 Diabetesen_US
dc.subjectType 1 Diabetes Genetic Risk Scoreen_US
dc.titleSystematic genetic testing for recessively inherited monogenic diabetes: a cross-sectional study in paediatric diabetes clinicsen_US
dc.typeArticleen_US

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