title: Coexistence of Mosaic Uniparental Isodisomy and a KCNJ11 Mutation Presenting as Diffuse Congenital Hyperinsulinism and Hemihypertrophy.
abstract: BACKGROUND
  Isolated hyperinsulinaemic hypoglycaemia (HH) commonly results from recessively inherited mutations in the ABCC8 and KCNJ11 genes that are located on chromosome 11p15.1. More rarely, HH can feature in patients with Beckwith-Wiedemann syndrome (BWS), a congenital overgrowth disorder, resulting from defects at a differentially methylated region telomeric to the K-ATP channel genes at chromosome 11p15.5.
  
  
  METHODS
  We undertook genetic testing in a patient with diazoxide-unresponsive HH diagnosed at birth. Physical examination later revealed hemihypertrophy of the right arm, a feature of BWS.
  
  
  RESULTS
  We identified a novel mosaic, paternally-inherited KCNJ11 mutation(s) in the patient. Further analysis confirmed uniparental disomy (UPD) of chromosome 11, which extended across the KCNJ11 gene at 11p15.1 and the BWS locus at 11p15.5.
  
  
  CONCLUSIONS
  These results highlight the importance of considering UPD as a mechanism of disease in patients with HH and a paternally inherited K-ATP channel mutation, especially when additional syndromic features are present.
authors.forename: Pınar
authors.initials: P
authors.lastname: Kocaay
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Şiklar
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Aydın
authors.initials: A
authors.lastname: Yagmurlu
authors.forename: Emine
authors.initials: E
authors.lastname: Çamtosun
authors.forename: Esra
authors.initials: E
authors.lastname: Erden
authors.forename: Merih
authors.initials: M
authors.lastname: Berberoglu
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Flanagan
mesh_terms: D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics* / Q000473:pathology; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D044903:Congenital Hyperinsulinism / Q000235:genetics* / Q000473:pathology; D005260:Female; D056426:Genetic Loci; D006801:Humans; D008297:Male; D009030:Mosaicism; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D024182:Uniparental Disomy / Q000235:genetics* / Q000473:pathology; D000099161:Kcnj11 Channel
chemical_list: D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel