Paternal uniparental isodisomy of chromosome 11 p 15.5 within the pancreas causes isolated hyperinsulinemic hypoglycemia

10Citations
Citations of this article
6Readers
Mendeley users who have this article in their library.

Abstract

Background: Loss of function mutations in the genes encoding the pancreatic β-cell ATP-sensitive potassium (KATP) channel are identified in approximately 80% of patients with diazoxide unresponsive hyperinsulinemic hypoglycemia (HH). For a small number of patients HH can occur as part of a multisystem disease such as Beckwith-Wiedemann syndrome (BWS). In approximately 20% of patients, BWS results from chromosome 11 paternal uniparental disomy (UPD), which causes dysregulation of imprinted growth regula- tion genes at 11 p 15.5.There is a considerable range in the clinical features and phenotypic severity associated with BWS which is likely to be due to somatic mosaicism. The cause of HH in these patients is not known. Research Design and Methods: We undertook microsatellite analysis of 12 markers spanning chromosome 11 p in two patients with severe HH and diffuse disease requiring a pancreatectomy. In both patients mutations in the KATP channel genes had not been identified. Results: We identified segmental paternal UPD in DNA extracted from pancreatic tissue in both patients. UPD was not observed in DNA extracted from the patient's leukocytes or buccal samples. In both cases the UPD encom- passed the differentially methylated region at chromosome 11 p 15.5. Despite this neither patient had any further features of BWS. Conclusion: Paternal UPD of the chromosome 11 p 15.5 differentially methylated region limited to the pancreatic tissue may represent a novel cause of isolated diazoxide unresponsive HH. Loss of heterozygosity studies should therefore be considered in all patients with severe HH who have undergone pancreatic surgery when KATP channel mutation(s) have not been identified. © 2011 Flanagan, Kapoor, Smith, Hussain and Ellard.

Cite

CITATION STYLE

APA

Flanagan, S. E., Kapoor, R. R., Smith, V. V., Hussain, K., & Ellard, S. (2011). Paternal uniparental isodisomy of chromosome 11 p 15.5 within the pancreas causes isolated hyperinsulinemic hypoglycemia. Frontiers in Endocrinology, 2(NOV). https://doi.org/10.3389/fendo.2011.00066

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free