title: Chromosome 11p15 paternal isodisomy in focal forms of neonatal hyperinsulinism.
abstract: BACKGROUND
  Focal forms of congenital hyperinsulinism are due to a constitutional heterozygous mutation of paternal origin in the ABCC8 gene, more often than the KCNJ11 gene, located in the 11p15.1 region. This mutation is associated with the loss of the maternally inherited 11p15.1 to 11p15.5 region in the lesion. We investigated the possible occurrence of a compensatory duplication of the paternal 11p15.1-11p15.5 region.
  
  
  METHODS
  A combined immunohistochemistry and fluorescent in situ hybridization study on beta-cell interphase nuclei with probes covering two genes located in this region (ABCC8 and CDKN1C genes) was performed in four cases of focal forms of hyperinsulinism.
  
  
  RESULTS
  beta-Cells in the lesions of four cases of focal congenital hyperinsulinism were diploid for chromosomes 11 and 13. The 11p15.1 to 11p15.2 and 11p15.4 to 11p15.5 regions containing ABCC8 and CDKN1C genes, respectively, were present with two copies. Loss of the maternal allele was confirmed in these focal lesions with microsatellite markers flanking the ABCC8 and CDKN1C genes, whereas a heterozygous mutation in the ABCC8 gene was inherited from the father.
  
  
  CONCLUSIONS
  There is a duplication of the paternal allele on chromosome 11 in the focal forms of hyperinsulinism lesion. The paternal isodisomy observed rendered the beta-cells homozygous for ABCC8 mutation and harbored a K-channel defect in the lesion similar to that observed in diffuse forms of congenital hyperinsulinism.
authors.affiliation: Department of Pathology, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Service d'Anatomie Pathologique and Tumorotheque, 149 rue de Sèvres, 75015 Paris, France. francis.jaubert@nck.aphp.fr
authors.forename: L
authors.initials: L
authors.lastname: Damaj
authors.forename: M
authors.initials: M
authors.lastname: le Lorch
authors.forename: V
authors.initials: V
authors.lastname: Verkarre
authors.forename: C
authors.initials: C
authors.lastname: Werl
authors.forename: L
authors.initials: L
authors.lastname: Hubert
authors.forename: C
authors.initials: C
authors.lastname: Nihoul-Fékété
authors.forename: Y
authors.initials: Y
authors.lastname: Aigrain
authors.forename: Y
authors.initials: Y
authors.lastname: de Keyzer
authors.forename: S P
authors.initials: SP
authors.lastname: Romana
authors.forename: C
authors.initials: C
authors.lastname: Bellanne-Chantelot
authors.forename: P
authors.initials: P
authors.lastname: de Lonlay
authors.forename: F
authors.initials: F
authors.lastname: Jaubert
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000483:Alleles; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D005220:Fathers; D006801:Humans; D006946:Hyperinsulinism / Q000151:congenital* / Q000235:genetics*; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D018895:Microsatellite Repeats; D011003:Ploidies; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D011955:Receptors, Drug / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064233:Sulfonylurea Receptors; D024182:Uniparental Disomy / Q000235:genetics*; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D004247:DNA; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel