ESPE2015 Poster Presentations Poster Category 1 Diabetes (33 abstracts)
Somatic Paternal UPD on Chromosome 11p15 in Focal Form of Congenital Hyperinsulinism (CHI) Causes Monoallelic Expression of Mutant ABCC8 and KCNJ11
Ina Dallmann a , Silke Vogelgesang b , Winfried Barthlen c , Emine Varol c , Wolfgang Mohnike d , Susann Empting e , Klaus Mohnike e , Martin Zenker a & Ilse Wieland a
aInstitute of Human Genetics, Otto-von-Guericke University, University Hospital, Magdeburg, Germany; bInstitute of Pathology, University Greifswald, Greifswald, Germany; cUniversity Greifswald, Clinic for Pediatric Surgery, Greifswald, Germany; dDTZ Berlin Am Frankfurter Tor, Berlin, Germany; eDepartment of Pediatrics, Otto-von-Guericke University, University Hospital, Magdeburg, Germany
Background: Congenital hyperinsulinism (CHI) is a disorder characterised by dysregulation of insulin secretion that leads to severe hypoglycaemia in neonates and infants. The focal form of CHI is caused by an autosomal recessive mutation in the genes ABCC8 or KCNJ11 inherited from the father and a second somatic event in the affected islet of Langerhans.
Objective: We report molecular genetic examination of focal pancreatic lesions of patients receiving therapeutic surgery in order to discover the genetic mechanisms in focal form of CHI.
Method: Patients were selected from the German Registry for Congenital Hyperinsulinism with proven ABCC8 or KCNJ11 mutations. Loss of heterozygosity (LOH) and gene expression levels were analysed by PCR, RT-PCR and Sanger sequencing in 11 patients with focal form of CHI. Deletions, duplications and uniparental isodisomy (UPD) were tested by methylation-specific MLPA (MS-MLPA).
Results: Complete and partial LOH was found in 10/11 focal lesions and monoallellic expression of the mutant ABCC8/KCNJ11 alleles was observed in all lesions. In contrast, there was no LOH detected in surrounding pancreatic tissue or blood cells. This supports somatic mosaicism specific in pancreatic beta cells. Both, ABCC8 and KCNJ11, are located in proximity to the Beckwith-Wiedemann imprinting control region on chromosome 11p15 that is also known for UPD. By MS-MLPA paternal UPD at 11p15 was detected in all samples showing LOH, whereas no deletion or duplication was found of this region.
Conclusion: In focal form of CHI monoallelic expression of mutant ABCC8/KCNJ11 is mainly caused by somatic paternal UPD 11p15.
Funding: MicroDissect GmbH (Spende:Somatische Mosaike # 995040).
Article tools
My recent searches
My recently viewed abstracts
Authors
ESPE Abstracts
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more