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Mutations and variants in the cohesion factor genes NIPBL , SMC1A , and SMC3 in a cohort of 30 unrelated patients with Cornelia de Lange syndrome

2010; Wiley; Volume: 152A; Issue: 4 Linguagem: Inglês

10.1002/ajmg.a.33348

1552-4833

Juan Pié, María Concepción Gil‐Rodríguez, Milagros Ciero, Eduardo López‐Viñas, María Pilar Ribate, María Arnedo, Matthew A. Deardorff, Beatriz Puisac, Jesús Legarreta, Juan Carlos De Karam, Encarnación Rubio Aranda, Inés Bueno, A Baldellou, Ma Teresa Calvo, Núria Casals, José L. Olivares, Ana Losada, Fausto G. Hegardt, Ian D. Krantz, Paulino Gómez‐Puertas, Feliciano J. Ramos,

Congenital limb and hand anomalies

Abstract Cornelia de Lange syndrome (CdLS) manifests facial dysmorphic features, growth and cognitive impairment, and limb malformations. Mutations in three genes ( NIPBL , SMC1A , and SMC3 ) of the cohesin complex and its regulators have been found in affected patients. Here, we present clinical and molecular characterization of 30 unrelated patients with CdLS. Eleven patients had mutations in NIPBL (37%) and three patients had mutations in SMC1A (10%), giving an overall rate of mutations of 47%. Several patients shared the same mutation in NIPBL (p.R827GfsX2) but had variable phenotypes, indicating the influence of modifiers in CdLS. Patients with NIPBL mutations had a more severe phenotype than those with mutations in SMC1A or those without identified mutations. However, a high incidence of palate defects was noted in patients with SMC1A mutations. In addition, we observed a similar phenotype in both male and female patients with SMC1A mutations. Finally, we report the first patient with an SMC1A mutation and the Sandifer complex. © 2010 Wiley‐Liss, Inc.