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Original Paper

Clinical and Genetic Evaluation of Patients with KATP Channel Mutations from the German Registry for Congenital Hyperinsulinism

Mohnike K.a · Wieland I.b · Barthlen W.c · Vogelgesang S.d · Empting S.a · Mohnike W.e · Meissner T.f · Zenker M.b

Author affiliations

aDepartment of Pediatrics and bInstitute of Human Genetics, Otto von Guericke University Magdeburg, Magdeburg, cClinic for Pediatric Surgery and dInstitute of Pathology, University Greifswald, Greifswald, eDTZ Berlin Am Frankfurter Tor, Berlin, and fDepartment of General Pediatrics, Neonatology and Pediatric Cardiology, University Children's Hospital Düsseldorf, Düsseldorf, Germany

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Horm Res Paediatr 2014;81:156-168

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: July 19, 2013
Accepted: October 03, 2013
Published online: January 07, 2014
Issue release date: April 2014

Number of Print Pages: 13
Number of Figures: 1
Number of Tables: 3

ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)

For additional information: https://www.karger.com/HRP

Abstract

Congenital hyperinsulinism (CHI) causes hypoglycemia due to irregular insulin secretion. In infants, a rapid diagnosis and appropriate management to avoid severe hypoglycemia is mandatory. CHI is a heterogeneous condition at the clinical and genetic level, and disease-causing genes have been identified in about half of the patients. The majority of mutations have been identified in the ABCC8 and KCNJ11 genes encoding subunits of the KATP channel responsible for two distinct histological forms. The diffuse form is caused by autosomal recessive or dominant inherited mutations, whereas the focal form is caused by a paternally transmitted recessive mutation and a second somatic event. We report on an unselected cohort of 136 unrelated patients from the German CHI registry. Mutations in either the ABCC8 or KCNJ11 gene were identified in 61 of these patients (45%). In total, 64 different mutations including 38 novel ones were detected in this cohort. We observed biparental (recessive) inheritance in 34% of mutation-positive patients, dominant inheritance in 11% and paternal transmission of a mutation associated with a focal CHI type in 38%. In addition, we observed inheritance patterns that do not exactly follow the classical recessive or dominant mode, further adding to the genetic complexity of this disease.

© 2014 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: July 19, 2013
Accepted: October 03, 2013
Published online: January 07, 2014
Issue release date: April 2014

Number of Print Pages: 13
Number of Figures: 1
Number of Tables: 3

ISSN: 1663-2818 (Print)
eISSN: 1663-2826 (Online)

For additional information: https://www.karger.com/HRP


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