This report describes Cornelia de Lange syndrome 2, a subtype of Cornelia de Lange syndrome. The human gene implicated is SMC1A, which encodes structural maintenance of chromosomes 1A, a member of the cohesin multiprotein complex required for sister chromatid cohesion. SMC1A is also associated with developmental and epileptic encephalopathy 85 (MIM:301044). There is one high-scoring fly ortholog, Dmel\SMC1, for which multiple genetic reagents, including an amorphic allele, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
The human gene SMC1A has not yet been introduced into flies.
Ubiquitous RNAi knockdown of Dmel\SMC1 resulted in an increase in startle response time, an increase in spontaneous locomotor activity, and a decrease in night sleep.
[updated July 2024 by FlyBase; FBrf0222196]
Cornelia de Lange syndrome (CDLS) is a multisystem malformation syndrome recognized primarily on the basis of characteristic facial dysmorphism, in association with prenatal and postnatal growth retardation, mental retardation and, in many cases, upper limb anomalies. However, there is wide clinical variability in this disorder, with milder phenotypes that may be difficult to ascertain on the basis of physical features (summary by Rohatgi et al., 2010; pubmed:20583156). [from MIM:122470; 2017.09.08]
[CORNELIA DE LANGE SYNDROME 2; CDLS2](https://omim.org/entry/300590)
[STRUCTURAL MAINTENANCE OF CHROMOSOMES 1A; SMC1A](https://omim.org/entry/300040)
See general description of Cornelia de Lange syndrome.
Cornelia de Lange syndrome-2 (CDLS2) is caused by mutation in the SMC1A gene, which encodes a subunit of the cohesin complex, on chromosome Xp11. [from MIM:300590; 2024.07.02]
Proper cohesion of sister chromatids is a prerequisite for the correct segregation of chromosomes during cell division. The cohesin multiprotein complex is required for sister chromatid cohesion. This complex is composed partly of two structural maintenance of chromosomes (SMC) proteins, SMC3 and either SMC1A or the SMC1B. 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. In addition, this protein interacts with BRCA1 and is phosphorylated by ATM, indicating a potential role for this protein in DNA repair. This gene, which belongs to the SMC gene family, is located in an area of the X-chromosome that escapes X inactivation. [provided by RefSeq, Jul 2013]
Two to one (2 human to 1 Drosophila); SMC1A has one high-scoring Drosophila ortholog, SMC1.
High-scoring ortholog of human SMC1A, SMC1B (1 Drosophila to 2 human).
