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GCK gene mutations are a common cause of childhood-onset MODY (maturity-onset diabetes of the young) in Turkey

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dc.contributor.authorBEREKET, ABDULLAH
dc.contributor.authorsHaliloglu, Belma; Hysenaj, Gerald; Atay, Zeynep; Guran, Tulay; Abali, Saygin; Turan, Serap; Bereket, Abdullah; Ellard, Sian
dc.date.accessioned2022-03-14T08:14:01Z
dc.date.available2022-03-14T08:14:01Z
dc.date.issued2016-09
dc.description.abstractObjectiveInactivating heterozygous mutations in the GCK gene are a common cause of MODY and result in mild fasting hyperglycaemia, which does not require treatment. We aimed to identify the frequency, clinical and molecular features of GCK mutations in a Turkish paediatric cohort. Design and PatientsFifty-four unrelated probands were selected based on the following criteria: age of diagnosis 17years, family history of diabetes in at least two generations, anti-GAD/ICA negative, BMI<95.p and follow-up with diet, oral antidiabetic drug or low-dose insulin treatment (05U/kg/d). A MODY probability score () was calculated and 21 patients with a score 75%, HbA1c levels 75% (585mmol/mol) and fasting blood glucose (FBG) levels 99-145mg/dl (55-80mmol/l) were selected for Sanger sequencing of the GCK gene. Targeted next-generation sequencing for all known monogenic diabetes genes was undertaken for any patient without a GCK gene mutation. ResultsGCK gene mutations (pathogenic or likely pathogenic variants) and a novel intronic variant of uncertain significance (c.208+3A>T) were identified in 13/54 probands (24%). Twelve of these patients had a MODY probability score 75%. FBG level and 2-h glucose level in OGTT were 12314mg/dl (68 +/- 07mmol/l) (107-157mg/dl) and 181 +/- 30mg/dl (101 +/- 16mmol/l) (136-247mg/dl), respectively. Average of glucose increment in OGTT was 58 +/- 27mg/dl (32 +/- 15mmol/l) (19-120mg/dl), and mean HbA1c level was 65 +/- 05% (475 +/- 55mmol/mol) (59-76%). Five novel missense mutations were identified (p.F123S, p.L58P, p.G246A, p.F419C, and p.S151C). Two patients treated with low-dose insulin before the molecular analysis were able to stop treatment. ConclusionsApproximately 1 in 4 MODY cases in this Turkish paediatric cohort have a GCK mutation. Selection of patients for GCK gene analysis using the MODY probability score was an effective way of identifying most (11/12) patients with a GCK mutation.
dc.identifier.doi10.1111/cen.13121
dc.identifier.eissn1365-2265
dc.identifier.issn0300-0664
dc.identifier.pubmed27256595
dc.identifier.urihttps://hdl.handle.net/11424/241187
dc.identifier.wosWOS:000383475800010
dc.language.isoeng
dc.publisherWILEY-BLACKWELL
dc.relation.ispartofCLINICAL ENDOCRINOLOGY
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectGLUCOKINASE MUTATIONS
dc.subjectPREVALENCE
dc.subjectCHILDREN
dc.subjectMELLITUS
dc.subjectDIAGNOSIS
dc.subjectFAMILIES
dc.subjectCAMPAIGN
dc.subjectCOHORT
dc.titleGCK gene mutations are a common cause of childhood-onset MODY (maturity-onset diabetes of the young) in Turkey
dc.typearticle
dspace.entity.typePublication
local.avesis.idadeea8f8-dc75-4b69-923a-bf768ad153a7
local.import.packageSS16
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages7
local.journal.quartileQ2
oaire.citation.endPage399
oaire.citation.issue3
oaire.citation.startPage393
oaire.citation.titleCLINICAL ENDOCRINOLOGY
oaire.citation.volume85
relation.isAuthorOfPublication669e9474-4e39-453f-a4bc-4ede9cb5abac
relation.isAuthorOfPublication.latestForDiscovery669e9474-4e39-453f-a4bc-4ede9cb5abac

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