title: Genetic heterogeneity for a Nijmegen breakage-like syndrome.
abstract: Nijmegen breakage syndrome (NBS) is a rare, autosomal-recessive chromosome instability disorder characterized by growth and developmental defects, immunodeficiency, high susceptibility to lymphoid malignancies, hypersensitivity to ionizing radiation and aberrant cell-cycle checkpoint control. The disease is caused by mutations in the NBS1 gene, which encodes nibrin, a component of the hMre11-Rad50-p95 complex involved in cellular response to DNA double-strand breaks. Genetic heterogeneity has been suggested in at least two patients with the NBS phenotype, but no mutation in the NBS1 gene; recently, mutations in the gene encoding the enzyme ligase IV have been identified in patients with signs of NBS. We describe a boy with an NBS clinical phenotype but no mutation in either the NBS1 or the LIG4 genes. The analysis of his cellular phenotype reveals chromosome instability and radiosensitivity, but normal cell-cycle checkpoint control. In addition, a literature review was carried out to summarize and compare data of all NBS-like patients reported to date. This case confirms genetic heterogeneity for NBS. We believe that dissecting the clinical and cellular phenotypes of this and other NBS-like patients will provide useful information for the research of new genes involved in cellular response to DNA damage and the assessment of cancer risk in NBS-like syndrome.
authors.affiliation: Biologia Generale e Genetica Medica, Università degli Studi di Pavia, Italy. marasc@unipv.it
authors.forename: P
authors.initials: P
authors.lastname: Maraschio
authors.forename: E
authors.initials: E
authors.lastname: Spadoni
authors.forename: C
authors.initials: C
authors.lastname: Tanzarella
authors.forename: A
authors.initials: A
authors.lastname: Antoccia
authors.forename: A
authors.initials: A
authors.lastname: Di Masi
authors.forename: M
authors.initials: M
authors.lastname: Maghnie
authors.forename: R
authors.initials: R
authors.lastname: Varon
authors.forename: I
authors.initials: I
authors.lastname: Demuth
authors.forename: L
authors.initials: L
authors.lastname: Tiepolo
authors.forename: C
authors.initials: C
authors.lastname: Danesino
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002675:Child, Preschool; D019457:Chromosome Breakage / Q000235:genetics*; D004252:DNA Mutational Analysis; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics; D013577:Syndrome
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins