title: Genome-wide expression analysis in fibroblast cell lines from probands with Pallister Killian syndrome.
abstract: Pallister Killian syndrome (OMIM: # 601803) is a rare multisystem disorder typically caused by tissue limited mosaic tetrasomy of chromosome 12p (isochromosome 12p). The clinical manifestations of Pallister Killian syndrome are variable with the most common findings including craniofacial dysmorphia, hypotonia, cognitive impairment, hearing loss, skin pigmentary differences and epilepsy. Isochromosome 12p is identified primarily in skin fibroblast cultures and in chorionic villus and amniotic fluid cell samples and may be identified in blood lymphocytes during the neonatal and early childhood period. We performed genomic expression profiling correlated with interphase fluorescent in situ hybridization and single nucleotide polymorphism array quantification of degree of mosaicism in fibroblasts from 17 Caucasian probands with Pallister Killian syndrome and 9 healthy age, gender and ethnicity matched controls. We identified a characteristic profile of 354 (180 up- and 174 down-regulated) differentially expressed genes in Pallister Killian syndrome probands and supportive evidence for a Pallister Killian syndrome critical region on 12p13.31. The differentially expressed genes were enriched for developmentally important genes such as homeobox genes. Among the differentially expressed genes, we identified several genes whose misexpression may be associated with the clinical phenotype of Pallister Killian syndrome such as downregulation of ZFPM2, GATA6 and SOX9, and overexpression of IGFBP2.
authors.affiliation: The Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Maninder
authors.initials: M
authors.lastname: Kaur
authors.affiliation: The Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America; Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Izumi
authors.affiliation: The Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Alisha B
authors.initials: AB
authors.lastname: Wilkens
authors.affiliation: Department of Pediatrics, Section of Pediatric Cardiology, The Children's Hospital of Colorado, Denver, Colorado, United States of America.
authors.forename: Kathryn C
authors.initials: KC
authors.lastname: Chatfield
authors.affiliation: The Department of Pathology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America; The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Nancy B
authors.initials: NB
authors.lastname: Spinner
authors.affiliation: The Department of Pathology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America; The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Conlin
authors.affiliation: Center for Biomedical Informatics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: The Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America; The Perelman School of Medicine at The University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Krantz
mesh_terms: D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D025063:Chromosome Disorders / Q000235:genetics* / Q000473:pathology*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D020732:Cytogenetic Analysis; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male