Back to Search
Start Over
Loss of imprinted genes and paternal SUR1 mutations lead to hyperinsulinism in focal adenomatous hyperplasia.
- Source :
-
Annales d'endocrinologie [Ann Endocrinol (Paris)] 1998; Vol. 59 (6), pp. 485-91. - Publication Year :
- 1998
-
Abstract
- Two types of histopathological lesions, a focal adenomatous hyperplasia of islet cells of the pancreas in about 30% of operated sporadic cases, and a diffuse form can be observed in congenital hyperinsulinism, or Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI). 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 which is 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. We now report somatic reduction to hemizygosity or homozygosity of a paternal SUR1 constitutional heterozygous mutation, in five patients with a focal form of PHHI. Thus this somatic event (LOH) which leads both to b 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.
- Subjects :
- Adenoma, Islet Cell genetics
Chromosomes, Human, Pair 11
Diazoxide therapeutic use
Drug Resistance
Humans
Hyperinsulinism complications
Hyperinsulinism surgery
Hyperplasia
Hypoglycemia complications
Infant, Newborn
Pancreatectomy
Pancreatic Neoplasms genetics
Polymerase Chain Reaction
Polymorphism, Single-Stranded Conformational
Sulfonylurea Receptors
ATP-Binding Cassette Transporters
Genomic Imprinting
Hyperinsulinism genetics
Hypoglycemia genetics
Islets of Langerhans pathology
Mutation
Potassium Channels genetics
Potassium Channels, Inwardly Rectifying
Receptors, Drug genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0003-4266
- Volume :
- 59
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Annales d'endocrinologie
- Publication Type :
- Academic Journal
- Accession number :
- 10189991