NIPBL, Encoding a Homolog of Fungal Scc2-type Sister Chromatid Cohesion Proteins and Fly Nipped-B, Is Mutated in Cornelia De Lange Syndrome

Nat Genet. 2004 Jun;36(6):636-41. doi: 10.1038/ng1363. Epub 2004 May 16.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics*
  • Chromosomal Proteins, Non-Histone
  • Chromosomes, Human, Pair 5 / genetics
  • DNA-Binding Proteins / genetics*
  • De Lange Syndrome / embryology
  • De Lange Syndrome / genetics*
  • De Lange Syndrome / 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

Substances

  • 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

Associated data

  • GENBANK/AJ627032
  • GENBANK/AJ627033
  • GENBANK/AJ627564
  • GENBANK/AJ640137
  • GENBANK/AJ640138
  • OMIM/268300