title: Deletion of the NESP55 differentially methylated region causes loss of maternal GNAS imprints and pseudohypoparathyroidism type Ib.
abstract: Epigenetic defects in the imprinted GNAS cluster are associated with pseudohypoparathyroidism type Ib. In two kindreds with this disorder, we now report deletions that remove the differentially methylated region encompassing exon NESP55 and exons 3 and 4 of the antisense transcript. When inherited from a female, either deletion abolishes all maternal GNAS imprints and derepresses maternally silenced transcripts, suggesting that the deleted region contains a cis-acting element that controls imprinting of the maternal GNAS allele.
authors.affiliation: Endocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. bastepe@helix.mgh.harvard.edu <bastepe@helix.mgh.harvard.edu>
authors.forename: Murat
authors.initials: M
authors.lastname: Bastepe
authors.forename: Leopold F
authors.initials: LF
authors.lastname: Fröhlich
authors.forename: Agnès
authors.initials: A
authors.lastname: Linglart
authors.forename: Hilal S
authors.initials: HS
authors.lastname: Abu-Zahra
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Tojo
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Ward
authors.forename: Harald
authors.initials: H
authors.lastname: Jüppner
mesh_terms: D001483:Base Sequence; D002864:Chromogranins; D019175:DNA Methylation; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics* / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011547:Pseudohypoparathyroidism / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
chemical_list: D002864:Chromogranins; D008565:Membrane Proteins; C490237:NNAT protein, human; D009419:Nerve Tissue Proteins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs