hrp0089rfc3.2 | Diabetes and Insulin 1 | ESPE2018

Personalized and Predictive Medicine for Pediatric Diabetes Through a Genetic Test Using Next Generation Sequencing

Schwitzgebel Valerie , Klee Philippe , Dirlewanger Mirjam , Blouin Jean-Louis

Introduction: Monogenic diabetes (MD) accounts for at least 3% of all pediatric diabetes cases. MD is often misdiagnosed as type 1 or type 2 diabetes, because of its wide phenotypic spectrum. While clinical and biochemical parameters can suggest MD, a definitive diagnosis requires genetic analysis. We conducted a broad study to diagnose MD cases. Then, with the gained knowledge, we designed a new diagnostic to...

hrp0086fc9.1 | Pathophysiology of Disorders of Insulin Secretion | ESPE2016

Next Generation Sequencing for the Diagnosis of Monogenic Diabetes in Switzerland

Klee Philippe , Dirlewanger Mirjam , Blouin Jean-Louis , Castellsague-Perolini Montserrat , Santoni Federico , Schwitzgebel Valerie

Background: Monogenic diabetes (MD) remains undiagnosed in more than 90% of the cases. However, precise, quick and cost-effective diagnosis is important to choose an adequate treatment and to avoid long-term complications.Objective and hypotheses: To develop and validate a diagnostic tool to improve diagnosis rate of MD in Switzerland, as well as to open new research directions.Method: Targeted next-generation sequencing (NGS) of 3...

hrp0082p1-d1-58 | Diabetes | ESPE2014

A leu402pro Mutation of the Non-hla Gene il18rap in Aggressive Neonatal Type 1 Diabetes Mellitus

Dirlewanger Mirjam , Blouin Jean-Louis , Bevillard Jeremy , Santoni Federico , Schwitzgebel Valerie

Background: Neonatal diabetes mellitus is defined by severe hyperglycemia appearing before 6 months of age. It occurs in about one in 200 000 live births and most cases are known to be of monogenic origin. Classical autoimmune type 1 diabetes mellitus (DM) is exceptional in this age group.Objective and hypotheses: Recently non-HLA type 1 DM susceptibility genes, such as IL18RAP, influencing the rate of progression to diabetes among children with...

hrp0084p1-33 | Diabetes | ESPE2015

Improved Genetic Testing for Monogenic Diabetes in the Swiss Population by Targeted Next Generation Sequencing

Dirlewanger Mirjam , Blouin Jean-Louis , Klee Philippe , Castellsague-Perolini Montserrat , Girardin Celine , Santoni Federico , Schwitzgebel Valerie

Background: Monogenic diabetes is a heterogeneous group of diabetes due to a single gene mutation and includes neonatal diabetes (NDM), MODY and rare forms of syndromic diabetes. These forms of diabetes remain undiagnosed in probably more than 90% of patients. The aim of the study was to identify mutations causing monogenic diabetes using a single test.Method: Swiss endocrinologists were proposed to participate in the study and to send blood samples of t...

hrp0092fc6.1 | Bone, Growth Plate and Mineral Metabolism Session 2 | ESPE2019

Bone Tissue Characterization of a Mouse Model of Atypical Type VI Osteogenesis Imperfecta Reveals Hypermineralization of the Bone Matrix, Elevated Osteocyte Lacunardensity and Altered Vascularity

Hedjazi Ghazal , Guterman-Ram Gali , Blouin Stéphane , Roschger Paul , Klaushofer Klaus , Fratzl-Zelman Nadja , Marini Joan C

Objectives: Osteogenesis imperfecta (OI) is an extremely heterogeneous connective tissue disorder characterized by low bone mass, which together with altered bone matrix properties leads to skeletal fragility. Due to the wide range of symptoms, the pathophysiology of the OI is not fully understood. Null mutations in SERPINF1, encoding the potent antiangiogenic factor PEDF, cause type VI OI with excessive osteoid formation, abnormal osteoblast-osteocyt...

hrp0086rfc9.4 | Pathophysiology of Disorders of Insulin Secretion | ESPE2016

Prevalence of Monogenic Diabetes in the Lithuanian Pediatric and Young Adult Population

Schwitzgebel Valerie , Dirlewanger Mirjam , Klee Philippe , Santoni Federico , Blouin Jean-Louis , Razanskaite-Virbickiene Dovile , Danyte Evalda , Dobrovolskiene Rimante , Marciulionyte Dalia , Stankute Ingrida , Verkauskiene Rasa

Background: Monogenic diabetes is a heterogeneous group of metabolic disorders resulting from defects in single genes. Over 90% of the subjects remain undiagnosed, mainly because of lack of access to genetic testing.Objective and hypotheses: The aim of our study was to do a comprehensive genetic analysis of the whole pediatric and young adult autoimmune antibody negative diabetes population of Lithuania.Method: 860 children (age 0&...