Naslov
The first report on MODY testing in children in Croatia

Autori
Špehar Uroić, Anita ; Merkler, Ana ; Krnić, Nevena ; Miličić, Iva ; Rojnić Putarek, Nataša ; Caban, Domagoj ; Sertić, Jadranka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Pediatric diabetes, 22 (2021), Suppl 30 / - , 2021, 146-146

Skup
47th Annual Conference of the International Society for Pediatric and Adolescent Diabetes (ISPAD 2021)

Mjesto i datum
Online, 13.10.2021. - 15.10.2021

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
MODY ; Sanger sequencing ; HNF1A ; GCK

Sažetak
Introduction:Maturity onset diabetes of the young (MODY) is a het-erogeneous group of autosomal dominant disorders that result inβ-cell dysfunction. It is often misdiagnosed as type 1 or type 2 diabe-tes. MODY-GCK is the most frequent form in children, followed byMODY resulting from HNF1A, HNF4A, and HNF1B gene mutations.Molecular diagnosis is essential because it leads to optimal treatmentand follow-up, frequently allowing cessation of therapy in childrenand often correction of diagnosis and treatment in their parents.Objectives:Molecular genetic testing for the four most frequentMODY types (GCK, HNF1A, HNF4A, and HNF1B) was introduced inCroatia in 2017. We present the first Croatian results of MODY test-ing in children.Methods:Children presenting with fasting hyperglycemia, impairedglucose tolerance or overt diabetes, with measurable C-peptide levelsand negative GAD and IA-2 antibodies, and preferably with a positivefamily history of hyperglycemia or diabetes were eligible for thegenetic analysis. TheGCK, HNF1A, HNF4A, andHNF1Bgenes wereanalyzed by Sanger sequencing.Results: Eighty-five children were referred to MODY testing (medianage 14 years (95%CI 12-15 years ; 61% M) ; 65 were tested forMODY-GCK (37 positives, 56, 9%) ; 24 for HNF1A (6 positives, 25.0%) ; 9 for HNF4A and 2 for HNF1B (no positive results). We identified17 different mutations in theGCKgene, the most common being p.Thr228Met in exon 7. We have detected two novel variants(c.736G>C, pGly246Arg, c.982G>T, p.Gly328*) in GCK and one(c.66delC, p.Ser22Arg*9) in the HNF1A gene, that we presumed to bepathogenic according to clinical presentation. Upon confirmation ofMODY-GCK, therapy was discontinued in nine patients.Conclusions:In agreement with the literature, MODY-GCK was thepredominant form of MODY in our children. The molecular diagnosisled to correction of therapy and follow-up regiment in children andsuggested correction of diagnosis and therapy in their affected parent.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

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