title: Screening of DNA methylation at the H19 promoter or the distal region of its ICR1 ensures efficient detection of chromosome 11p15 epimutations in Russell-Silver syndrome.
abstract: Over a 10-year period blood samples were collected from 57 individuals with growth restriction and RSS-like features. Our goal was to identify epigenetic abnormalities in this cohort, including uniparental disomy of chromosome 7 (UPD7), methylation changes at chromosome 11p15, as well as new epigenomic alterations. We evaluated the methylation status of 7 imprinting control regions on chromosomes 7, 11, 14, and 15. UPD7 and chromosome 7 structural abnormalities had been previously identified in five patients. Epigenetic alterations on chromosome 11p15 were identified in 11 patients. Of interest, in 3 of these 11 patients, the epigenetic alterations were limited to the H19 promoter and the distal region of its associated imprinting center, ICR1. In addition, in one patient, we detected methylation changes consistent with maternal UPD at all tested imprinted regions. This patient series suggests that epimutations on chromosome 11p15 can be most efficiently detected in RSS patients by screening for DNA methylation defects at the H19 promoter or the distal region of ICR.
authors.affiliation: Program in Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Horike
authors.forename: Jose Carlos P
authors.initials: JC
authors.lastname: Ferreira
authors.forename: Makiko
authors.initials: M
authors.lastname: Meguro-Horike
authors.forename: Sanaa
authors.initials: S
authors.lastname: Choufani
authors.forename: Adam C
authors.initials: AC
authors.lastname: Smith
authors.forename: Cheryl
authors.initials: C
authors.lastname: Shuman
authors.forename: Wendy
authors.initials: W
authors.lastname: Meschino
authors.forename: David
authors.initials: D
authors.lastname: Chitayat
authors.forename: Elaine
authors.initials: E
authors.lastname: Zackai
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.forename: Rosanna
authors.initials: R
authors.lastname: Weksberg
mesh_terms: D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D004247:DNA / Q000097:blood / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D008297:Male; D009030:Mosaicism; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D056730:Silver-Russell Syndrome / Q000097:blood / Q000235:genetics*
chemical_list: C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D004247:DNA