title: A case report of a patient with microcephaly, facial dysmorphism, chromosomal radiosensitivity and telomere length alterations closely resembling "Nijmegen breakage syndrome" phenotype.
abstract: Genetic heterogeneity in Nijmegen breakage syndrome (NBS) is highlighted by patients showing clinical and cellular features of NBS but with no mutations in NBS1 and normal levels of nibrin. NBS is an autosomal recessive disorder, whose clinical cellular signs include growth and developmental defects, dysmorphic facies, immunodeficiency, cancer predisposition, chromosomal instability and radiosensitivity. NBS is caused by mutations in the NBS1 gene, whose product is part of the MRE11/RAD50/NBS1 complex involved in the DNA double-strand break (DSB) response pathway. Since the identification of the NBS1 gene, patients with NBS clinical signs, particularly severe congenital microcephaly, are screened for mutations in the NBS1 gene. Further analyses include X-ray-induced chromosome aberrations, telomere analysis, kinetics of DSBs repair, levels of a panel of proteins involved in the maintenance of genetic stability, radiation-induced phosphorylation of various substrates and cell cycle analysis. We describe a patient with a NBS clinical phenotype, chromosomal sensitivity to X-rays but without mutations in the whole NBS1 or in the Cernunnos gene. Enhanced response to irradiation was mediated neither by DSBs rejoining defects nor by the NBS/AT-dependent DNA-damage response pathway. Notably, we found that primary fibroblasts from this patient displayed telomere length alterations. Cross-talk between pathways controlling response to DSBs and those involved in maintaining telomeres has been shown in the present patient. Dissecting the cellular phenotype of radiosensitive NBS-like patients represents a useful tool for the research of new genes involved in the cellular response to DSBs.
authors: Department of Biology, University Roma Tre, V le Marconi 446, Rome, Italy.
authors: F
authors: F
authors: Berardinelli
authors: A
authors: A
authors: di Masi
authors: M
authors: M
authors: Salvatore
authors: S
authors: S
authors: Banerjee
authors: K
authors: K
authors: Myung
authors: J P
authors: JP
authors: De Villartay
authors: P
authors: P
authors: Revy
authors: A
authors: A
authors: Plebani
authors: A
authors: A
authors: Soresina
authors: D
authors: D
authors: Taruscio
authors: C
authors: C
authors: Tanzarella
authors: A
authors: A
authors: Antoccia
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics; D002877:Chromosomes, Human / Q000528:radiation effects; D019465:Craniofacial Abnormalities / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D049932:Nijmegen Breakage Syndrome / Q000175:diagnosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D010641:Phenotype; D011836:Radiation Tolerance / Q000235:genetics*; D016615:Telomere / Q000235:genetics* / Q000648:ultrastructure
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins