title: Elevation of insulin-like growth factor binding protein-2 level in Pallister-Killian syndrome: implications for the postnatal growth retardation phenotype.
abstract: Pallister-Killian syndrome (PKS) is a multi-system developmental disorder caused by tetrasomy 12p that exhibits tissue-limited mosaicism. Probands with PKS often demonstrate a unique growth profile consisting of macrosomia at birth with deceleration of growth postnatally. We have previously demonstrated that cultured skin fibroblasts from PKS probands have significantly elevated expression of insulin-like growth factor binding protein-2 (IGFBP2). To further evaluate the role of IGFBP2 in PKS, the amount of IGFBP2 secreted from cultured skin fibroblast cell lines and serum IGFBP2 levels were measured in probands with PKS. Approximately 60% of PKS fibroblast cell lines secreted higher levels of IGFBP2 compared to control fibroblasts, although the remaining 40% of PKS samples produced comparable level of IGFBP2 to that of control fibroblasts. Serum IGFBP2 levels were also measured in PKS probands and were elevated in 40% of PKS probands. PKS probands with elevated IGFBP2 manifested with severe postnatal growth retardation. IGFBPs are the family of related proteins that bind IGFs with high affinity and are typically thought to attenuate IGF action. We suggest that elevated IGFBP2 levels might play a role in the growth retardation phenotype of PKS.
authors.affiliation: Divisionof Human Genetics, The Children Hospital of Philadelphia, Philadelphia, Pennsylvania.|Research Center for Epigenetic Disease, Institute for Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Izumi
authors.affiliation: Divisionof Human Genetics, The Children Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Emily
authors.initials: E
authors.lastname: Kellogg
authors.affiliation: Research Center for Epigenetic Disease, Institute for Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Fujiki
authors.affiliation: Divisionof Human Genetics, The Children Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Maninder
authors.initials: M
authors.lastname: Kaur
authors.affiliation: Divisionof Human Genetics, The Children Hospital of Philadelphia, Philadelphia, Pennsylvania.|Temple University School of Medicine, Philadelphia, Pennsylvania.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Tilton
authors.affiliation: Divisionof Human Genetics, The Children Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Sarah
authors.initials: S
authors.lastname: Noon
authors.affiliation: Divisionof Human Genetics, The Children Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Alisha
authors.initials: A
authors.lastname: Wilkens
authors.affiliation: Research Center for Epigenetic Disease, Institute for Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.affiliation: Divisionof Human Genetics, The Children Hospital of Philadelphia, Philadelphia, Pennsylvania.|The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Krantz
mesh_terms: D016022:Case-Control Studies; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000097:blood / Q000235:genetics* / Q000473:pathology; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D019175:DNA Methylation; D002658:Developmental Disabilities / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D007621:Karyotyping; D008297:Male; D009030:Mosaicism; D010641:Phenotype; D011401:Promoter Regions, Genetic
chemical_list: C577903:IGFBP2 protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2
keywords: growth retardation; isochromosome 12p; mosaicism