CDKN1C (p57(Kip2)) analysis in Beckwith-Wiedemann syndrome (BWS) patients: Genotype-phenotype correlations, novel mutations, and polymorphisms.
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.
Romanelli
Valeria
V
INGEMM, Instituto de Genética Médica y Molecular, IdiPAZ-Hospital Universitario La Paz, Universidad Autónoma de Madrid, Madrid, Spain.
Belinchón
Alberta
A
Benito-Sanz
Sara
S
Martínez-Glez
Victor
V
Gracia-Bouthelier
Ricardo
R
Heath
Karen E
KE
Campos-Barros
Angel
A
García-Miñaur
Sixto
S
Fernandez
Luís
L
Meneses
Heloisa
H
López-Siguero
Juan Pedro
JP
Guillén-Navarro
Encarna
E
Gómez-Puertas
Paulino
P
Wesselink
Jan-Jaap
JJ
Mercado
Graciela
G
Esteban-Marfil
Victoria
V
Palomo
Rebeca
R
Mena
Rocío
R
Sánchez
Aurora
A
Del Campo
Miguel
M
Lapunzina
Pablo
P
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
C493964:CDKN1C protein, human; D050761:Cyclin-Dependent Kinase Inhibitor p57