Mutations in the SMC1A gene are responsible for a form of Cornelia de Lange syndrome (Cornelia de Lange syndrome 2; OMIM 300590), a clinically heterogeneous developmental disorder characterized by malformations affecting multiple systems (Deardorff et al., 2007). Phenotypic characterization of 51 individuals with SMC1A variants demonstrated that 6/6 individuals displayed socialization deficits (ranging from mild to profound) and 20/31 individuals (65%) exhibited stereotypic movements (Huisman et al., 2017); furthermore, 5 females from a cohort of 13 Dutch individuals with SMC1A variants presented with a phenotype similar to Rett syndrome: epileptic encephalopathy, severe or profound intellectual disability, stereotypic movements, and, in some cases, developmental regression.
The cohesin multiprotein complex is required for sister chromatid cohesion, a prerequisite for the correct segregation of chromosomes during cell division, and is composed partly of two structural maintenance of chromosomes (SMC) proteins: SMC3 and either SMC1B or the protein encoded by this gene. Most of the cohesin complexes dissociate from the chromosomes before mitosis, although those complexes at the kinetochore remain. Therefore, the encoded protein is thought to be an important part of functional kinetochores.
Type of Disorder
Phenotypes and genotypes in individuals with SMC1A variants.