This report describes Cornelia de Lange syndrome 1 (CDLS1), which is a subtype of Cornelia de Lange syndrome; CDLS1 exhibits autosomal dominant inheritance. The human gene implicated in this disease is NIPBL, cohesion loading factor, which contributes to the function of the Cohesion complex, which, in turn, ensures sister chromatid cohesion prior to segregation during mitosis or meiosis II. There is a single orthologous gene in Drosophila, Nipped-B, for which loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
The human NIPBL gene has not been introduced into flies.
Animals homozygous for loss-of-function mutations of Dmel\Nipped-B die during the larval stage; 50% of metaphase nuclei in the brains of second instar larvae show precocious sister chromatid separation. Nipped-B heterozygous mutant animals show reduced growth, defects in learning and memory, altered circadian rhythms, and morphological abnormalities in brain structure. Genetic and physical interactions of Dmel\Nipped-B have been described; see below and in the Nipped-B gene report.
[updated Sep. 2017 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 1; CDLS1](https://omim.org/entry/122470)
[NIPPED-B-LIKE; NIPBL](https://omim.org/entry/608667)
See general description of Cornelia de Lange syndrome.
Cornelia de Lange syndrome-1 (CDLS1) is caused by heterozygous mutation in the NIPBL gene; about 50-60% of cases of CDLS are of this type. [from MIM:122470; 2017.09.08]
Cohesin is a protein complex required for sister chromatid cohesion prior to segregation during mitosis or meiosis II. NIPBL forms a dimer with MAU2 that is essential for loading the cohesin complex onto sister chromatids. [from MIM:608667; 2017.09.08]
One to one: 1 human to 1 Drosophila.
High-scoring ortholog of human gene NIPBL (1 Drosophila to 1 human); Dmel\Nipped-B shares 27% identity and 42% similarity with the human gene.
