hrp0082fc3.4 | Diabetes | ESPE2014

Genetics of Paediatric Type 2 Diabetes: ABCC8 Mutation in Obesity-Associated Insulin Secretion Defects

Wiegand Susanna , Simaite Deimante , Dannemann Almut , Kuhnen Peter , Krude Heiko , Gong Maolian , Raile Klemens

Background: Type 2 diabetes in children and adolescents is a rare disease with an estimated incidence (age 0–20 years) of below 5/100 000 in Germany.Objective and Hypotheses: We hypothesize that monogenic alterations might contribute to early-onset insulin secretion defects, if islet function was challenged by obesity-associated insulin resistance.Method: We follow more than 1500 children and adolescents with obesity. Patients...

hrp0082fc9.3 | Beta cells | ESPE2014

In Search for New Monogenic Diabetes Genes: PCBD1

Simaite Deimante , Kofent Julia , Gong Maolian , Ruschendorf Franz , Jia Shiqi , Arn Pamela , Bentler Kristi , Ellaway Carolyn , Kuhnen Peter , Hoffmann Georg , Blau Nenad , Spagnoli Francesca , Hubner Norbert , Raile Klemens

Background: Mutations in more than 20 genes are described to cause monogenic diabetes. Nevertheless, numerous families with diabetes of unknown ethology and suspected genetic defect have no molecular diagnosis. This not only impedes our understanding of disease mechanisms but also prevents from predicting the clinical course of the patients and applying the pathogenesis-oriented treatment.Objective: To identify novel gene(s), causing monogenic adolescent...

hrp0084fc3.3 | Diabetes | ESPE2015

Clinical Characteristics and Molecular Genetic Analysis of Six Patients with Pancreas Aplasia and Neonatal Diabetes: Predominance of PTF1A-Enhancer Mutations

Raile Klemens , Gong Maolian , Spagnoli Francesca , Chen Wei , Hummel Oliver , Darendeliler Feiza , Bober Ece , Abaci Ayhan , Krill Winfried , Thiel Susanne , Kuhnen Peter , Hussain Khalid

Background: Pancreas aplasia (PA) and neonatal diabetes mellitus (NDM) syndrome is a rare disease that usually presents in the 1st months of life.Objective and hypotheses: We aimed to characterize molecular genetic defects in a cohort of six NDM/PA patients with up-to-date unknown pathogenesis with optimum genetic testing.Method: As part of our ESPE-RU-project ‘Understanding the molecular basis of diabetes mellitus associated ...

hrp0092fc15.2 | Late Breaking Abstracts | ESPE2019

HDAC4 Mutations Cause Diabetes and Induce β-Cell FoxO1 Nuclear Exclusion

Gong Maolian , Yu Yong , Vuralli Dogus , Fröhler Sebastian , Kühnen Peter , Du Bois Philipp , Zhang Jingjing , Hussain Khalid , Fielitz Jens , Jia Shiqi , Chen Wei , Raile Klemens

Background: Studying patients with rare Mendelian diabetes has highlighted molecular mechanisms regulating β-cell pathophysiology. Previous, experimental studies have shown that Class IIa histone deacetylases (HDAC4, 5, 7, and 9) modulate mammalian pancreatic endocrine cell differentiation, function and finally glucose homeostasis.Methods: We performed exome sequencing in one adolescent boy with non-autoimmune di...

hrp0086ha1 | KCNQ1 Mutations Cause Both Neonatal Diabetes and Hyperinsulinemic Hypoglycaemia of Infancy | ESPE2016

KCNQ1 Mutations Cause Both Neonatal Diabetes and Hyperinsulinemic Hypoglycaemia of Infancy

Liang Lei , Jia Shiqi , Frohler Sebastian , Kuhnen Peter , Blankenstein Oliver , Krill Winfried , Khodaverdi Semik , Cao Aidi , Hummel Oliver , Elbarbary Nancy , Hussain Khalid , Voelkl Jacob , Chen Wei , Gong Maolian , Raile Klemens

Background: Mutations in genes involved in insulin secretion or regulation of β cell identity cause both persistent neonatal diabetes (PND) and hyperinsulinemic hypoglycemia of infancy (HHI) pinpointing shared pathogenic mechanisms. KCNQ1 encodes a potassium channel protein, Kv7.1, which is a voltage-gated potassium channel expressed in cardiac tissue, pancreas, inner ear neurons, and other tissues. Variants in or nearby to KCNQ1 were linked t...