Advertisement

Research Article Free access | 10.1172/JCI4495

Paternal mutation of the sulfonylurea receptor (SUR1) gene and maternal loss of 11p15 imprinted genes lead to persistent hyperinsulinism in focal adenomatous hyperplasia.

V Verkarre, J C Fournet, P de Lonlay, M S Gross-Morand, M Devillers, J Rahier, F Brunelle, J J Robert, C Nihoul-Fékété, J M Saudubray, and C Junien

INSERM UR 383, Hôpital Necker-Enfants Malades, University Paris V, 75743 Paris Cedex 15, France.

Find articles by Verkarre, V. in: JCI | PubMed | Google Scholar

INSERM UR 383, Hôpital Necker-Enfants Malades, University Paris V, 75743 Paris Cedex 15, France.

Find articles by Fournet, J. in: JCI | PubMed | Google Scholar

INSERM UR 383, Hôpital Necker-Enfants Malades, University Paris V, 75743 Paris Cedex 15, France.

Find articles by de Lonlay, P. in: JCI | PubMed | Google Scholar

INSERM UR 383, Hôpital Necker-Enfants Malades, University Paris V, 75743 Paris Cedex 15, France.

Find articles by Gross-Morand, M. in: JCI | PubMed | Google Scholar

INSERM UR 383, Hôpital Necker-Enfants Malades, University Paris V, 75743 Paris Cedex 15, France.

Find articles by Devillers, M. in: JCI | PubMed | Google Scholar

INSERM UR 383, Hôpital Necker-Enfants Malades, University Paris V, 75743 Paris Cedex 15, France.

Find articles by Rahier, J. in: JCI | PubMed | Google Scholar

INSERM UR 383, Hôpital Necker-Enfants Malades, University Paris V, 75743 Paris Cedex 15, France.

Find articles by Brunelle, F. in: JCI | PubMed | Google Scholar

INSERM UR 383, Hôpital Necker-Enfants Malades, University Paris V, 75743 Paris Cedex 15, France.

Find articles by Robert, J. in: JCI | PubMed | Google Scholar

INSERM UR 383, Hôpital Necker-Enfants Malades, University Paris V, 75743 Paris Cedex 15, France.

Find articles by Nihoul-Fékété, C. in: JCI | PubMed | Google Scholar

INSERM UR 383, Hôpital Necker-Enfants Malades, University Paris V, 75743 Paris Cedex 15, France.

Find articles by Saudubray, J. in: JCI | PubMed | Google Scholar

INSERM UR 383, Hôpital Necker-Enfants Malades, University Paris V, 75743 Paris Cedex 15, France.

Find articles by Junien, C. in: JCI | PubMed | Google Scholar

Published October 1, 1998 - More info

Published in Volume 102, Issue 7 on October 1, 1998
J Clin Invest. 1998;102(7):1286–1291. https://doi.org/10.1172/JCI4495.
© 1998 The American Society for Clinical Investigation
Published October 1, 1998 - Version history
View PDF
Abstract

Congenital hyperinsulinism, or persistent hyperinsulinemic hypoglycemia of infancy (PHHI), is a glucose metabolism disorder characterized by unregulated secretion of insulin and profound hypoglycemia. From a morphological standpoint, there are two types of histopathological lesions, a focal adenomatous hyperplasia of islet cells of the pancreas in approximately 30% of operated sporadic cases, and a diffuse form. In sporadic focal forms, specific losses of maternal alleles (LOH) of the imprinted chromosomal region 11p15, restricted to the hyperplastic area of the pancreas, were observed. Similar mechanisms are observed in embryonal tumors and in the Beckwith-Wiedemann syndrome (BWS), also associated with neonatal but transient hyperinsulinism. However, this region also contains the sulfonylurea receptor (SUR1) gene and the inward rectifying potassium channel subunit (KIR6.2) gene, involved in recessive familial forms of PHHI, but not known to be imprinted. Although the parental bias in loss of maternal alleles did not argue in favor of their direct involvement, the LOH may also unmask a recessive mutation leading to persistent hyperinsulinism. We now report somatic reduction to hemizygosity or homozygosity of a paternal SUR1 constitutional heterozygous mutation in four patients with a focal form of PHHI. Thus, this somatic event which leads both to beta cell proliferation and to hyperinsulinism can be considered as the somatic equivalent, restricted to a microscopic focal lesion, of constitutional uniparental disomy associated with unmasking of a heterozygous parental mutation leading to a somatic recessive disorder.

Version history
  • Version 1 (October 1, 1998): No description
Advertisement
Advertisement