Journal ArticleDOI
Maturity onset diabetes of youth (MODY) in Turkish children: sequence analysis of 11 causative genes by next generation sequencing.
Sebahat Yılmaz Ağladıoğlu,Zehra Aycan,Semra Çetinkaya,Veysel Nijat Baş,Aşan Önder,Havva Nur Peltek Kendirci,Haldun Dogan,Serdar Ceylaner +7 more
TLDR
GCK is the most frequent type of MODY in the study population, supports that in heterogenous disorders like MODY sequence analysis provides rapid, cost effective and accurate genetic diagnosis.Abstract:
BACKGROUND Maturity-onset diabetes of the youth (MODY), is a genetically and clinically heterogeneous group of diseasesand is often misdiagnosed as type 1 or type 2 diabetes. The aim of this study is to investigate both novel and proven mutations of 11 MODY genes in Turkish children by using targeted next generation sequencing. METHODS A panel of 11 MODY genes were screened in 43 children with MODY diagnosed by clinical criterias. Studies of index cases was done with MISEQ-ILLUMINA, and family screenings and confirmation studies of mutations was done by Sanger sequencing. RESULTS We identified 28 (65%) point mutations among 43 patients. Eighteen patients have GCK mutations, four have HNF1A, one has HNF4A, one has HNF1B, two have NEUROD1, one has PDX1 gene variations and one patient has both HNF1A and HNF4A heterozygote mutations. CONCLUSIONS This is the first study including molecular studies of 11 MODY genes in Turkish children. GCK is the most frequent type of MODY in our study population. Very high frequency of novel mutations (42%) in our study population, supports that in heterogenous disorders like MODY sequence analysis provides rapid, cost effective and accurate genetic diagnosis.read more
Citations
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Journal ArticleDOI
Clinical features, complications and treatment of rarer forms of maturity-onset diabetes of the young (MODY) - A review
Ramasamy Aarthy,Kathryn Aston-Mourney,Antonina Mikocka-Walus,Venkatesan Radha,Anandakumar Amutha,Ranjit Mohan Anjana,Ranjit Unnikrishnan,Viswanathan Mohan +7 more
TL;DR: The clinical characteristics of the rare MODY subtypes exhibited heterogeneity between families reported with the same mutation, and obesity and diabetic ketoacidosis were also reported among rarer MODy subtypes which presents as a challenge as these are not part of the original description of MODY.
Journal ArticleDOI
Targeted next generation sequencing in patients with maturity-onset diabetes of the young (MODY).
Taha Reşid Özdemir,Ozgur Kirbiyik,Bumin Dündar,Ayhan Abaci,Ozge Ozer Kaya,Gönül Çatlı,Berk Ozyilmaz,Sezer Acar,Altuğ Koç,Merve Saka Guvenc,Yasar B. Kutbay,Kadri Murat Erdoğan +11 more
TL;DR: Most of the variants in MODY genes found in the GCK gene in patients with MODY were revealed using targeted next generation sequencing (NGS), which allows simultaneous analysis of multiple genes in a single panel.
Journal ArticleDOI
Permanent neonatal diabetes mellitus and neurological abnormalities due to a novel homozygous missense mutation in NEUROD1.
Huseyin Demirbilek,Nihal Hatipoglu,Ulku Gul,Zeynep Uzan Tatlı,Sian Ellard,Sarah E. Flanagan,Elisa De Franco,Selim Kurtoglu +7 more
TL;DR: It is currently unclear whether the NEUROD1 heterozygous mutation has contributed to diabetes development in these individuals, but the third case of PNDM with neurological abnormalities caused by homozygous NEurOD1 mutation is reported.
Journal ArticleDOI
Whole‑exome sequencing in Russian children with non‑type 1 diabetes mellitus reveals a wide spectrum of genetic variants in MODY‑related and unrelated genes
Oleg S. Glotov,Elena A. Serebryakova,Mariia E. Turkunova,Olga A. Efimova,Andrey S. Glotov,Yury A. Barbitoff,Yulia A. Nasykhova,Alexander V. Predeus,Dmitrii E. Polev,Mikhail A. Fedyakov,Irina V. Polyakova,T. E. Ivashchenko,Natalia Yu. Shved,Elena S. Shabanova,Alena V. Tiselko,Olga V. Romanova,Andrey M. Sarana,Anna A. Pendina,Sergey G. Scherbak,Ekaterina V. Musina,Anastasiia V. Petrovskaia‑Kaminskaia,Liubov R. Lonishin,Liliya V. Ditkovskaya,Liudmila А. Zhelenina,Ludmila V. Tyrtova,Olga Berseneva,Rostislav K. Skitchenko,Evgenii N. Suspitsin,Elena B. Bashnina,V. S. Baranov +29 more
TL;DR: The prevalence of GCK variants indicates that diagnostics of monogenic diabetes in Russian children may begin with testing for MODY2, highlighting the efficiency of using whole-exome sequencing in non-GCK-MODY cases.
Journal ArticleDOI
Analysis of the GCK gene in 79 MODY type 2 patients: A multicenter Turkish study, mutation profile and description of twenty novel mutations.
Ayca Aykut,Emin Karaca,Hüseyin Onay,Damla Gökşen,Şevki Çetinkalp,Erdal Eren,Betül Ersoy,Esra Deniz Papatya Cakir,Muammer Buyukinan,Cengiz Kara,Ahmet Anık,Birgül Kirel,Samim Özen,Tahir Atik,Şükran Darcan,Ferda Ozkinay +15 more
TL;DR: The aim of this study was to evaluate the molecular spectrum of GCK gene mutations in 177 Turkish MODY type 2 patients and identify mutant alleles, including 45 different GCK mutations, 20 of which were novel.
References
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TL;DR: The regional distribution of confirmed MODY cases in the UK is compared and the minimum prevalence is estimated to be 108 cases per million, assuming >80% of MODY is not diagnosed by molecular testing.
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NeuroD is required for differentiation of the granule cells in the cerebellum and hippocampus
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Journal ArticleDOI
Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes
TL;DR: It is proposed that the old clinical classifications of maturity-onset diabetes of the young and neonatal diabetes are obsolete and that specific genetic etiologies should be sought in four broad clinical situations because of their specific treatment implications.