title: Mutations and variants in the cohesion factor genes NIPBL, SMC1A, and SMC3 in a cohort of 30 unrelated patients with Cornelia de Lange syndrome.
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.
authors.affiliation: Laboratory of Clinical Genetics and Functional Genomics, Department of Pharmacology, Medical School, University of Zaragoza, Zaragoza, Spain. juanpie@unizar.es
authors.forename: Juan
authors.initials: J
authors.lastname: Pié
authors.forename: María Concepción
authors.initials: MC
authors.lastname: Gil-Rodríguez
authors.forename: Milagros
authors.initials: M
authors.lastname: Ciero
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Viñas
authors.forename: María Pilar
authors.initials: MP
authors.lastname: Ribate
authors.forename: María
authors.initials: M
authors.lastname: Arnedo
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Deardorff
authors.forename: Beatriz
authors.initials: B
authors.lastname: Puisac
authors.forename: Jesús
authors.initials: J
authors.lastname: Legarreta
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: de Karam
authors.forename: Encarnación
authors.initials: E
authors.lastname: Rubio
authors.forename: Inés
authors.initials: I
authors.lastname: Bueno
authors.forename: Antonio
authors.initials: A
authors.lastname: Baldellou
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Calvo
authors.forename: Nuria
authors.initials: N
authors.lastname: Casals
authors.forename: José Luis
authors.initials: JL
authors.lastname: Olivares
authors.forename: Ana
authors.initials: A
authors.lastname: Losada
authors.forename: Fausto G
authors.initials: FG
authors.lastname: Hegardt
authors.forename: Ian D
authors.initials: ID
authors.lastname: Krantz
authors.forename: Paulino
authors.initials: P
authors.lastname: Gómez-Puertas
authors.forename: Feliciano J
authors.initials: FJ
authors.lastname: Ramos
mesh_terms: D000483:Alleles; D018797:Cell Cycle Proteins / Q000235:genetics*; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D015331:Cohort Studies; D003635:De Lange Syndrome / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D018797:Cell Cycle Proteins; D011508:Chondroitin Sulfate Proteoglycans; D002868:Chromosomal Proteins, Non-Histone; C487465:NIPBL protein, human; D011506:Proteins; C492318:SMC3 protein, human; D000098550:Structural Maintenance of Chromosome Protein 1