title: Hepatoblastoma in a child with a paternally-inherited ABCC8 mutation and mosaic paternal uniparental disomy 11p causing focal congenital hyperinsulinism.
abstract: Hepatoblastoma is a tumour of early childhood occurring in association with genetic syndromes including Beckwith-Wiedemann Syndrome (BWS) which results from dominance of paternally-inherited genes on chromosome 11p15. We report a child without clinical BWS, neonatally diagnosed with focal congenital hyperinsulinism resulting from a paternally-inherited recessively-acting mutation of ABCC8 and pancreatic paternal uniparental disomy (UPD) for chromosome 11p15, who subsequently developed hepatoblastoma. Genetic testing showed UPD 11p15 in the pancreas and liver but not systemically, allowing the expression of mutated ABCC8 in both tissues. Infants with large or multifocal forms of focal congenital hyperinsulinism may be at risk of BWS-like tumours due to mosaic UPD despite negative whole-blood and buccal DNA testing and tumour surveillance should be considered for this minority.
authors.affiliation: Department of Paediatric Oncology, University Hospital Southampton Foundation Trust, Southampton, UK. libbycalton@cix.co.uk
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Calton
authors.forename: I Karen
authors.initials: IK
authors.lastname: Temple
authors.forename: Deborah J G
authors.initials: DJ
authors.lastname: Mackay
authors.forename: Margaret
authors.initials: M
authors.lastname: Lever
authors.forename: Sian
authors.initials: S
authors.lastname: Ellard
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Flanagan
authors.forename: Justin H
authors.initials: JH
authors.lastname: Davies
authors.forename: Khalid
authors.initials: K
authors.lastname: Hussain
authors.forename: Juliet C
authors.initials: JC
authors.lastname: Gray
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11; D044903:Congenital Hyperinsulinism / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D018197:Hepatoblastoma / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D007223:Infant; D008113:Liver Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D009030:Mosaicism; D009154:Mutation; D049268:Positron-Emission Tomography; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011955:Receptors, Drug / Q000235:genetics*; D064233:Sulfonylurea Receptors; D014057:Tomography, X-Ray Computed; D024182:Uniparental Disomy
chemical_list: D018528:ATP-Binding Cassette Transporters; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors