Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-KATP channel mutations

Basit Öğe Kaydı
dc.contributor.authorDemirbilek, Huseyin
dc.contributor.authorArya, Ved Bhushan
dc.contributor.authorNuri, Mehmet
dc.contributor.authorHoughton, Jayne A. L.
dc.contributor.authorBaran, Riza Taner
dc.contributor.authorAkar, Melek
dc.contributor.authorTekes, Selahattin
dc.date.accessioned2024-04-24T17:18:03Z
dc.date.available2024-04-24T17:18:03Z
dc.date.issued2015
dc.departmentDicle Üniversitesien_US
dc.description.abstractBackground: Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes and usually presents in the first 6 months of life. We aimed to describe the clinical characteristics and molecular genetics of a large Turkish cohort of NDM patients from a single centre and estimate an annual incidence rate of NDM in South-Eastern Anatolian region of Turkey. Design and methods: NDM patients presenting to Diyarbakir Children State Hospital between 2010 and 2013, and patients under follow-up with presumed type 1 diabetes mellitus, with onset before 6 months of age were recruited. Molecular genetic analysis was performed. Results: Twenty-two patients (59% males) were diagnosed with NDM (TNDM-5; PNDM-17). Molecular genetic analysis identified a mutation in 20 (95%) patients who had undergone a mutation analysis. In transient neonatal diabetes (TNDM) patients, the genetic cause included chromosome 6q24 abnormalities (n=3), ABCC8 (n=1) and homozygous INS (n=1). In permanent neonatal diabetes (PNDM) patients, homozygous GCK (n=6), EIF2AK3 (n=3), PTF1A (n=3), and INS (n=1) and heterozygous KCNJ11 (n=2) mutations were identified. Pancreatic exocrine dysfunction was observed in patients with mutations in the distal PTF1A enhancer. Both patients with a KCNJ11 mutation responded to oral sulphonylurea. A variable phenotype was associated with the homozygous c.-331C>A INS mutation, which was identified in both a PNDM and TNDM patient. The annual incidence of PNDM in South-East Anatolian region of Turkey was one in 48 000 live births. Conclusions: Homozygous mutations in GCK, EIF2AK3 and the distal enhancer region of PTF1A were the commonest causes of NDM in our cohort. The high rate of detection of a mutation likely reflects the contribution of new genetic techniques (targeted next-generation sequencing) and increased consanguinity within our cohort.en_US
dc.description.sponsorshipWellcome Trust; Diabetes UK; European Society for Paediatric Endocrinology (ESPE); Scientific and Technological Research Council of Turkey (TUBITAK); Medical Research Council [MR/M023265/1] Funding Source: researchfish; National Institute for Health Research [NF-SI-0611-10219] Funding Source: researchfish; MRC [MR/M023265/1] Funding Source: UKRIen_US
dc.description.sponsorshipThe genetic testing was funded by the Wellcome Trust (Senior Investigator Award to Profs S Ellard and A T Hattersley), and by Diabetes UK (Project funding to Dr D J Mackay). H Demirbilek was funded by European Society for Paediatric Endocrinology (ESPE) and The Scientific and Technological Research Council of Turkey (TUBITAK) for his 1 year clinical fellowship at University College London (UCL), Institute of Child Health, Great Ormond Street Hospital for Children, NHS Trust, Department of Paediatric Endocrinology.en_US
dc.identifier.doi10.1530/EJE-14-0852
dc.identifier.endpage705en_US
dc.identifier.issn0804-4643
dc.identifier.issn1479-683X
dc.identifier.issue6en_US
dc.identifier.pmid25755231
dc.identifier.scopus2-s2.0-84930607319
dc.identifier.scopusqualityQ1
dc.identifier.startpage697en_US
dc.identifier.urihttps://doi.org/10.1530/EJE-14-0852
dc.identifier.urihttps://hdl.handle.net/11468/18573
dc.identifier.volume172en_US
dc.identifier.wosWOS:000357212600013
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoenen_US
dc.publisherBioscientifica Ltden_US
dc.relation.ispartofEuropean Journal of Endocrinology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject[No Keyword]en_US
dc.titleClinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-KATP channel mutationsen_US
dc.titleClinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-KATP channel mutations
dc.typeArticleen_US

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayın Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu