title: Clinical features of maternal uniparental disomy 14 in patients with an epimutation and a deletion of the imprinted DLK1/GTL2 gene cluster.
abstract: Maternal uniparental disomy 14 [upd(14)mat] is associated with a recognizable phenotype that includes pre- and postnatal growth retardation, neonatal hypotonia, feeding problems and precocious puberty. Chromosome 14 contains an imprinted gene cluster, which is regulated by a differentially methylated region (IG-DMR) between DLK1 and GTL2. Here we report on four patients with clinical features of upd(14)mat who show a maternal-only methylation pattern, but biparental inheritance for chromosome 14. In three of the patients loss of paternal methylation appears to be a primary epimutation, whereas the other patient has a paternally derived deletion of -1 Mb that includes the imprinted DLK1-GTL2 gene cluster. These findings demonstrate that the upd(14)mat phenotype is caused by altered expression of genes within this cluster.
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany. karin.buiting@uni-due.de
authors.forename: Karin
authors.initials: K
authors.lastname: Buiting
authors.forename: Deniz
authors.initials: D
authors.lastname: Kanber
authors.forename: José I
authors.initials: JI
authors.lastname: Martín-Subero
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.forename: Paulien
authors.initials: P
authors.lastname: Terhal
authors.forename: Beate
authors.initials: B
authors.lastname: Albrecht
authors.forename: Sabine
authors.initials: S
authors.lastname: Purmann
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gross
authors.forename: Christina
authors.initials: C
authors.lastname: Lich
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Bernhard
authors.initials: B
authors.lastname: Horsthemke
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gillessen-Kaesbach
mesh_terms: D000328:Adult; D002135:Calcium-Binding Proteins; D002648:Child; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic; D005260:Female; D017353:Gene Deletion; D018392:Genomic Imprinting; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009035:Mothers; D005810:Multigene Family; D009154:Mutation; D011506:Proteins; D062085:RNA, Long Noncoding; D024182:Uniparental Disomy / Q000235:genetics* / Q000503:physiopathology
chemical_list: D002135:Calcium-Binding Proteins; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C498907:MEG3 non-coding RNA, human; D008565:Membrane Proteins; D011506:Proteins; D062085:RNA, Long Noncoding