CDKN1C (p57Kip2) analysis in Beckwith-Wiedemann syndrome (BWS) patients: Genotype-phenotype correlations, novel mutations, and polymorphisms

• Published in: American journal of medical genetics. Part A 2010-06, Vol.152A (6), p.1390-1397
• Main Authors: Romanelli, Valeria, Belinchón, Alberta, Benito-Sanz, Sara, Martínez-Glez, Victor, Gracia-Bouthelier, Ricardo, Heath, Karen E., Campos-Barros, Angel, García-Miñaur, Sixto, Fernandez, Luís, Meneses, Heloisa, López-Siguero, Juan Pedro, Guillén-Navarro, Encarna, Gómez-Puertas, Paulino, Wesselink, Jan-Jaap, Mercado, Graciela, Esteban-Marfil, Victoria, Palomo, Rebeca, Mena, Rocío, Sánchez, Aurora, del Campo, Miguel, Lapunzina, Pablo
• Format: Article
• Language: English
• Subjects: Adult; Beckwith-Wiedemann Syndrome - genetics; Biological and medical sciences; Child; Child, Preschool; cleft palate; Cyclin-Dependent Kinase Inhibitor p57 - chemistry; Cyclin-Dependent Kinase Inhibitor p57 - genetics; Diseases of the osteoarticular system; extra nipple; Facial bones, jaws, teeth, parodontium: diseases, semeiology; Female; Genotype; Humans; Infant; Male; Malformations and congenital and or hereditary diseases involving bones. Joint deformations; Medical genetics; Medical sciences; Mutation; mutations; Non tumoral diseases; omphalocele; Otorhinolaryngology. Stomatology; overgrowth syndrome; Phenotype; polydactyly; Polymorphism, Genetic; Protein Conformation
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.33453

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. © 2010 Wiley‐Liss, Inc.