Mutations in Cohesin Complex Members SMC3 and SMC1A Cause a Mild Variant of Cornelia de Lange Syndrome with Predominant Mental Retardation

摘要: Mutations in the cohesin regulators NIPBL and ESCO2 are causative of Cornelia de Lange syndrome (CdLS) Roberts or SC phocomelia syndrome, respectively. Recently, mutations complex structural component SMC1A have been identified two probands with features CdLS. Here, we report identification a mutation gene encoding complementary subunit heterodimer, SMC3, 14 additional mutations. All predicted to retain an open reading frame, no truncating were identified. Structural analysis mutant SMC3 proteins indicate that all likely produce functional complexes, but posit they may alter their chromosome binding dynamics. Our data (1) contribute ∼5% cases CdLS, (2) result consistently mild phenotype absence major anomalies typically associated (3) some instances, approaches apparently nonsyndromic mental retardation.