NIPBL, encoding a homolog of fungal Scc2-type sister chromatid cohesion proteins and fly Nipped-B, is mutated in Cornelia de Lange syndrome.

Abstract	Cornelia de Lange syndrome (CdLS) is a multiple malformation disorder characterized by dysmorphic facial features, mental retardation, growth delay and limb reduction defects. We indentified and characterized a new gene, NIPBL, that is mutated in individuals with CdLS and determined its structure and the structures of mouse, rat and zebrafish homologs. We named its protein product delangin. Vertebrate delangins have substantial homology to orthologs in flies, worms, plants and fungi, including Scc2-type sister chromatid cohesion proteins, and D. melanogaster Nipped-B. We propose that perturbed delangin function may inappropriately activate DLX genes, thereby contributing to the proximodistal limb patterning defects in CdLS. Genome analyses typically identify individual delangin or Nipped-B-like orthologs in diploid animal and plant genomes. The evolution of an ancestral sister chromatid cohesion protein to acquire an additional role in developmental gene regulation suggests that there are parallels between CdLS and Roberts syndrome.
Authors	Emma T Tonkin, Tzu-Jou Wang, Steven Lisgo, Michael J Bamshad, Tom Strachan
Journal	Nature genetics (Nat Genet) Vol. 36 Issue 6 Pg. 636-41 (Jun 2004) ISSN: 1061-4036 [Print] United States
PMID	15146185 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Cell Cycle Proteins Chromosomal Proteins, Non-Histone DNA-Binding Proteins Drosophila Proteins NIPBL protein, human Proteins SCC2 protein, S cerevisiae Saccharomyces cerevisiae Proteins nipped-B protein, Drosophila
Topics	Animals Cell Cycle Proteins (genetics) Chromosomal Proteins, Non-Histone Chromosomes, Human, Pair 5 (genetics) DNA-Binding Proteins (genetics) De Lange Syndrome (embryology, genetics, pathology) Drosophila Proteins (genetics) Gene Expression Regulation, Developmental Humans In Situ Hybridization, Fluorescence Molecular Sequence Data Mutation Phenotype Proteins (genetics) Saccharomyces cerevisiae Proteins (genetics) Species Specificity

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