title: CDKN1C (p57(Kip2)) analysis in Beckwith-Wiedemann syndrome (BWS) patients: Genotype-phenotype correlations, novel mutations, and polymorphisms.
abstract: Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome characterized by macroglossia, macrosomia, and abdominal wall defects. It is a multigenic disorder caused in most patients by alterations in growth regulatory genes. A small number of individuals with BWS (5-10%) have mutations in CDKN1C, a cyclin-dependent kinase inhibitor of G1 cyclin complexes that functions as a negative regulator of cellular growth and proliferation. Here, we report on eight patients with BWS and CDKN1C mutations and review previous reported cases. We analyzed 72 patients (50 BWS, 17 with isolated hemihyperplasia (IH), three with omphalocele, and two with macroglossia) for CDKN1C defects with the aim to search for new mutations and to define genotype-phenotype correlations. Our findings suggest that BWS patients with CDKN1C mutations have a different pattern of clinical malformations than those with other molecular defects. Polydactyly, genital abnormalities, extra nipple, and cleft palate are more frequently observed in BWS with mutations in CDKN1C. The clinical observation of these malformations may help to decide which genetic characterization should be undertaken (i.e., CDKN1C screening), thus optimizing the laboratory evaluation for BWS.
authors.affiliation: INGEMM, Instituto de Genética Médica y Molecular, IdiPAZ-Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Valeria
authors.initials: V
authors.lastname: Romanelli
authors.forename: Alberta
authors.initials: A
authors.lastname: Belinchón
authors.forename: Sara
authors.initials: S
authors.lastname: Benito-Sanz
authors.forename: Victor
authors.initials: V
authors.lastname: Martínez-Glez
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gracia-Bouthelier
authors.forename: Karen E
authors.initials: KE
authors.lastname: Heath
authors.forename: Angel
authors.initials: A
authors.lastname: Campos-Barros
authors.forename: Sixto
authors.initials: S
authors.lastname: García-Miñaur
authors.forename: Luís
authors.initials: L
authors.lastname: Fernandez
authors.forename: Heloisa
authors.initials: H
authors.lastname: Meneses
authors.forename: Juan Pedro
authors.initials: JP
authors.lastname: López-Siguero
authors.forename: Encarna
authors.initials: E
authors.lastname: Guillén-Navarro
authors.forename: Paulino
authors.initials: P
authors.lastname: Gómez-Puertas
authors.forename: Jan-Jaap
authors.initials: JJ
authors.lastname: Wesselink
authors.forename: Graciela
authors.initials: G
authors.lastname: Mercado
authors.forename: Victoria
authors.initials: V
authors.lastname: Esteban-Marfil
authors.forename: Rebeca
authors.initials: R
authors.lastname: Palomo
authors.forename: Rocío
authors.initials: R
authors.lastname: Mena
authors.forename: Aurora
authors.initials: A
authors.lastname: Sánchez
authors.forename: Miguel
authors.initials: M
authors.lastname: Del Campo
authors.forename: Pablo
authors.initials: P
authors.lastname: Lapunzina
mesh_terms: D000328:Adult; D001506:Beckwith-Wiedemann Syndrome / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D011487:Protein Conformation
chemical_list: C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57