Nijmegen breakage syndrome: clinical manifestation of defective response to DNA double-strand breaks.
Nijmegen breakage syndrome is a rare autosomal recessive genetic disease belonging to a group of disorders often called chromosome instability syndromes. In addition to a characteristic facial appearance and microcephaly, patients suffering from Nijmegen breakage syndrome have a range of symptoms including radiosensitivity, immunodeficiency, increased cancer risk and growth retardation. The underlying gene, NBS1, is located on human chromosome 8q21 and codes for a protein product termed nibrin, Nbs1 or p95. Over 90% of patients are homozygous for a founder mutation: a deletion of five base pairs which leads to a framehift and protein truncation. The protein nibrin/Nbs1 is suspected to be involved in the cellular response to DNA damage caused by ionising irradiation, thus accounting for the radiosensitivity of Nijmegen breakage syndrome. We review here some of the more recent findings on the NBS1 gene and discuss how they impinge on the clinical manifestation of the disease.
Institute of Human Genetics, Charité-University Medicine Berlin, Augustenburger platz 1, Berlin 13353, Germany. martin.digweed@charite.de
Martin
M
Digweed
Karl
K
Sperling
D018797:Cell Cycle Proteins / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000648:ultrastructure; D004249:DNA Damage; D019066:Facies; D016368:Frameshift Mutation; D020022:Genetic Predisposition to Disease; D006130:Growth Disorders / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics; D008223:Lymphoma / Q000235:genetics; D008540:Meiosis; D008831:Microcephaly / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics; D011839:Radiation, Ionizing; D012306:Risk; D013577:Syndrome
D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins