title: Somatic mosaicism for maternal uniparental disomy 15 in a girl with Prader-Willi syndrome: confirmation by cell cloning and identification of candidate downstream genes.
abstract: Although uniparental disomy often results from the postzygotic rescue of a meiotic non-disjunction event, mosaicism is usually confined to the placenta. We describe a girl with Prader-Willi syndrome (PWS) who is mosaic for normal cells and cells with maternal uniparental disomy 15 [upd(15)mat] in blood and skin. Somatic mosaicism was confirmed by cloning and genotyping of skin fibroblasts. X inactivation studies indicated that upd occurred prior to X inactivation. RNA samples from the cloned cells were used in DNA microarray experiments to study the effect of upd(15)mat on the gene expression pattern of fibroblasts. Proof of principle was obtained by detecting several chromosome 15 genes known to be imprinted. We did not obtain any evidence for novel 15q genes showing imprinted expression in fibroblasts. Differentially expressed genes on other chromosomes are candidates for downstream genes regulated by an imprinted gene and may play a role in the pathogenesis of PWS. The finding of strongly reduced mRNA levels in upd(15)mat cells of the gene encoding secretogranin II (SCG2), which is a precursor of the dopamine releasing factor secretoneurin, raises the question whether hyperphagia in patients with PWS might be due to a defect in dopamine-modulated food reward circuits.
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany. b.horsthemke@uni-essen.de
authors.forename: Bernhard
authors.initials: B
authors.lastname: Horsthemke
authors.forename: Hülya
authors.initials: H
authors.lastname: Nazlican
authors.forename: Johannes
authors.initials: J
authors.lastname: Hüsing
authors.forename: Ludger
authors.initials: L
authors.lastname: Klein-Hitpass
authors.forename: Uwe
authors.initials: U
authors.lastname: Claussen
authors.forename: Susanne
authors.initials: S
authors.lastname: Michel
authors.forename: Christina
authors.initials: C
authors.lastname: Lich
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gillessen-Kaesbach
authors.forename: Karin
authors.initials: K
authors.lastname: Buiting
mesh_terms: D000328:Adult; D000483:Alleles; D002675:Child, Preschool; D002875:Chromosomes / Q000648:ultrastructure; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D003001:Cloning, Molecular; D004247:DNA / Q000737:chemistry; D019175:DNA Methylation; D004298:Dopamine / Q000378:metabolism; D004303:Dosage Compensation, Genetic; D005347:Fibroblasts / Q000378:metabolism; D018392:Genomic Imprinting; D005838:Genotype; D006801:Humans; D018895:Microsatellite Repeats; D020411:Oligonucleotide Array Sequence Analysis; D010920:Placenta / Q000378:metabolism; D011218:Prader-Willi Syndrome / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism; D024182:Uniparental Disomy
chemical_list: D012333:RNA, Messenger; D004247:DNA; D004298:Dopamine