title: Mosaic paternal genome-wide uniparental isodisomy with down syndrome.
abstract: We report on a 6-month-old girl with two apparent cell lines; one with trisomy 21, and the other with paternal genome-wide uniparental isodisomy (GWUPiD), identified using single nucleotide polymorphism (SNP) based microarray and microsatellite analysis of polymorphic loci. The patient has Beckwith-Wiedemann syndrome (BWS) due to paternal uniparental disomy (UPD) at chromosome location 11p15 (UPD 11p15), which was confirmed through methylation analysis. Hyperinsulinemic hypoglycemia is present, which is associated with paternal UPD 11p15.5; and she likely has medullary nephrocalcinosis, which is associated with paternal UPD 20, although this was not biochemically confirmed. Angelman syndrome (AS) analysis was negative but this testing is not completely informative; she has no specific features of AS. Clinical features of this patient include: dysmorphic features consistent with trisomy 21, tetralogy of Fallot, hemihypertrophy, swirled skin hyperpigmentation, hepatoblastoma, and Wilms tumor. Her karyotype is 47,XX,+21[19]/46,XX[4], and microarray results suggest that the cell line with trisomy 21 is biparentally inherited and represents 40-50% of the genomic material in the tested specimen. The difference in the level of cytogenetically detected mosaicism versus the level of mosaicism observed via microarray analysis is likely caused by differences in the test methodologies. While a handful of cases of mosaic paternal GWUPiD have been reported, this patient is the only reported case that also involves trisomy 21. Other GWUPiD patients have presented with features associated with multiple imprinted regions, as does our patient.
authors.affiliation: Silicon Valley Genetics Center, Santa Clara Valley Medical Center, San Jose, California.
authors.forename: Diana
authors.initials: D
authors.lastname: Darcy
authors.affiliation: Stanford University Medical Center, Palo Alto, California.
authors.forename: Paldeep Singh
authors.initials: PS
authors.lastname: Atwal
authors.affiliation: Neonatology, O'Connor Hospital, San Jose, California.
authors.forename: Cathy
authors.initials: C
authors.lastname: Angell
authors.affiliation: Laboratory Corporation of America, Research Triangle Park, North Carolina.
authors.forename: Inder
authors.initials: I
authors.lastname: Gadi
authors.affiliation: Silicon Valley Genetics Center, Santa Clara Valley Medical Center, San Jose, California.
authors.forename: Robert
authors.initials: R
authors.lastname: Wallerstein
mesh_terms: D001506:Beckwith-Wiedemann Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002880:Chromosomes, Human, Pair 11; D055028:Comparative Genomic Hybridization; D044903:Congenital Hyperinsulinism / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation; D004314:Down Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D015894:Genome, Human; D018392:Genomic Imprinting; D006801:Humans; D007223:Infant; D059785:Karyotype; D009030:Mosaicism; D020641:Polymorphism, Single Nucleotide; D024182:Uniparental Disomy / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
keywords: Beckwith-Wiedemann; SNP based microarray; UPD; genome-wide uniparental isodisomy; hemihypertrophy; mosaic; tetralogy of Fallot; uniparental disomy