De novo mutations of Emphasis Type="Italic"GCK/

Authors: Juraj Stanik Petra Dusatkova Ondrej Cinek Lucia Valentinova Miroslava Huckova Martina Skopkova Lenka Dusatkova Daniela Stanikova Mikulas Pura Iwar Klimes Jan Lebl Daniela Gasperikova Stepanka Pruhova

Publish Date: 2013/12/10

Volume: 57, Issue: 3, Pages: 480-484

PDF Link

Abstract

MODY is mainly characterised by an early onset of diabetes and a positive family history of diabetes with an autosomal dominant mode of inheritance However de novo mutations have been reported anecdotally The aim of this study was to systematically revisit a large collection of MODY patients to determine the minimum prevalence of de novo mutations in the most prevalent MODY genes ie GCK HNF1A HNF4AAnalysis of 922 patients from two national MODY centres Slovakia and the Czech Republic identified 150 probands 16 who came from pedigrees that did not fulfil the criterion of two generations with diabetes but did fulfil the remaining criteria The GCK HNF1A and HNF4A genes were analysed by direct sequencingMutations in GCK HNF1A or HNF4A genes were detected in 58 of 150 individuals Parents of 28 probands were unavailable for further analysis and in 19 probands the mutation was inherited from an asymptomatic parent In 11 probands the mutations arose de novoIn our cohort of MODY patients from two national centres the de novo mutations in GCK HNF1A and HNF4A were present in 73 of the 150 families without a history of diabetes and 12 of all of the referrals for MODY testing This is the largest collection of de novo MODY mutations to date and our findings indicate a much higher frequency of de novo mutations than previously assumed Therefore genetic testing of MODY could be considered for carefully selected individuals without a family history of diabetesWe would like to thank all of the attending diabetologists of the patients in the Czech Republic and Slovakia particularly Lubomir Barak and Emilia Jancova from the Children Diabetes Centre Bratislava Slovakia Beata Milosovicova from the Pediatric Endocrinology Outpatient Clinic Bratislava Slovakia We are also grateful to Martina Balogova Ivica Masindova Dominika Balaziova and Alica Mitkova from the DIABGENE Laboratory Institute of Experimental Endocrinology Bratislava Slovakia and Klara Vesela and Petra Peldova 2nd Faculty of Medicine Charles University in Prague Czech Republic for technical supportThis work was supported by research grants of the DIABGENE Laboratory Transendogen/26240220051 which is supported by the Research Development Operational Programme and funded by the European Regional Development Fund and Scientific Grant Agency of the Ministry of Education Science Research and Sport of the Slovak Republic 2/0151/11 This study was also supported by grants from the Czech Ministry of Health NT11402 and MH CZ–DRO University Hospital Motol Prague the Czech Republic 00064203All authors contributed to the study design and reviewed the manuscript critically and approved the final version JS and PD researched data and wrote the manuscript OC wrote the manuscript LD DS LV and MH researched data and MS MP IK JL DG and SP reviewed/edited the manuscript

Keywords: