title: Beckwith-Wiedemann syndrome in sibs discordant for IC2 methylation.
abstract: Genetically heterogeneous imprinting disorders include Beckwith-Wiedemann syndrome (BWS) and multiple maternal hypomethylation syndrome (MMHS). Using DNA sequencing, quantitative PCR, SNuPE, pyrosequencing, and hybridization to the Illumina GoldenGate Methylation Cancer Panel 1 array, we characterized the genomic DNA of two brothers with BWS who were discordant for loss of methylation at several differentially methylated regions (DMR), including imprinting center 2 (IC2) on chromosome band 11p15.5, which is often hypomethylated in BWS. In keeping with MMHS, the elder child had hypomethylation of SGCE and PLAGL1 as well as of IC2, whereas the younger brother demonstrated no loss of methylation at these DMRs. Although this discordance is consistent with the observation that 15-20% of individuals with BWS do not have detectable genetic or epigenetic alterations of 11p15.5, this is the first report of familial recurrence of BWS with discordance for chromosomal 11p15.5 alterations. We hypothesize that this apparent discordance arises either from mosaicism precluding identification of IC2 hypomethylation in blood or buccal mucosa DNA of the younger child, or from hypomethylation at a site not interrogated by our molecular studies.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
authors.forename: Karen Y
authors.initials: KY
authors.lastname: Niederhoffer
authors.forename: Maria
authors.initials: M
authors.lastname: Peñaherrera
authors.forename: Denise
authors.initials: D
authors.lastname: Pugash
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Rupps
authors.forename: Laura
authors.initials: L
authors.lastname: Arbour
authors.forename: Francine
authors.initials: F
authors.lastname: Tessier
authors.forename: Sanaa
authors.initials: S
authors.lastname: Choufani
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhao
authors.forename: Irina
authors.initials: I
authors.lastname: Manokhina
authors.forename: Cheryl
authors.initials: C
authors.lastname: Shuman
authors.forename: Wendy P
authors.initials: WP
authors.lastname: Robinson
authors.forename: Rosanna
authors.initials: R
authors.lastname: Weksberg
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Boerkoel
mesh_terms: D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11; D019175:DNA Methylation; D018392:Genomic Imprinting; D006801:Humans; D007223:Infant; D008297:Male; D018895:Microsatellite Repeats