Positional Cloning of the Gene for Nijmegen Breakage Syndrome

Nat Genet. 1998 Jun;19(2):179-81. doi: 10.1038/549.

Abstract

Nijmegen breakage syndrome (NBS), also known as ataxia-telangiectasia (AT) variant, is an autosomal recessive disorder characterized by microcephaly, growth retardation, severe combined immunodeficiency and a high incidence of lymphoid cancers. Cells from NBS patients display chromosome instability, hypersensitivity to ionizing radiation and abnormal cell-cycle regulation after irradiation, all of which are characteristics shared with AT. Recently, the NBS locus was mapped at 8q21 by two independent approaches, complementation studies and linkage analysis. Here, we report the positional cloning of the NBS gene, NBS1, from an 800-kb candidate region. The gene comprises 50 kb and encodes a protein of 754 amino acids. The amino-terminal region of the protein shows weak homology to the yeast XRS2, MEK1, CDS1 and SPK1 proteins. The gene is expressed at high levels in the testes, suggesting that it might be involved in meiotic recombination. We detected the same 5-bp deletion in 13 individuals, and conclude that it is likely to be a founder mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Ataxia Telangiectasia / genetics*
  • Cell Cycle Proteins / genetics*
  • Chromosome Breakage / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 8*
  • Cloning, Molecular
  • Databases, Factual
  • Growth Disorders / genetics
  • Humans
  • Microcephaly / genetics
  • Molecular Sequence Data
  • Nuclear Proteins*
  • Pedigree
  • Severe Combined Immunodeficiency / genetics
  • Syndrome

Substances

  • Cell Cycle Proteins
  • NBN protein, human
  • Nuclear Proteins

Associated data

  • GENBANK/AB013139