title: SMC1A codon 496 mutations affect the cellular response to genotoxic treatments.
abstract: Cornelia de Lange syndrome is a pleiotropic developmental syndrome characterized by growth and cognitive impairment, facial dysmorphic features, limb anomalies, and other malformations. Mutations in core cohesin genes SMC1A and SMC3, and the cohesin regulatory gene, NIPBL, have been identified in Cornelia de Lange syndrome probands. Patients with NIPBL mutations have more severe phenotypes when compared to those with mutations in SMC1A or SMC3. To date, 26 distinct SMC1A mutations have been identified in patients with Cornelia de Lange syndrome. Here, we describe a 3-year-old girl with psychomotor and cognitive impairment, mild facial dysmorphic features but no limb anomaly, heterozygous for a c.1487G>A mutation in SMC1A which predicts p.Arg496His. We show that this mutation leads to an impairment of the cellular response to genotoxic treatments.
authors.affiliation: Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Pisa, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Mannini
authors.forename: Stefania
authors.initials: S
authors.lastname: Menga
authors.forename: Alessandra
authors.initials: A
authors.lastname: Tonelli
authors.forename: Silvia
authors.initials: S
authors.lastname: Zanotti
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bassi
authors.forename: Cinzia
authors.initials: C
authors.lastname: Magnani
authors.forename: Antonio
authors.initials: A
authors.lastname: Musio
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics*; D002460:Cell Line; D002675:Child, Preschool; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D003062:Codon; D004249:DNA Damage; D003635:De Lange Syndrome / Q000235:genetics*; D005260:Female; D006579:Heterozygote; D006801:Humans; D009154:Mutation; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D003062:Codon; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1