Nijmegen Breakage Syndrome
Patrick J Concannon, PhD and Richard A Gatti, MD, GeneReviews, June 14, 2005
 [for Professionals mainly]
[NBS, Berlin Breakage Syndrome (BBS), Seemanova Syndrome, Ataxia-telangiectasia Complementation Group V1 or V2], Patrick J. Concannon, PhD; Richard A. Gatti, MD, April 20, 1999 … (NBS) is characterized by short stature, progressive microcephaly with loss of cognitive skills, ovarian failure in females, recurrent sinopulmonary infections, and an increased risk for cancer, particularly lymphoma … DNA-based testing of the NBS1 gene (chromosomal locus 8q21) detects disease-causing mutations in almost 100% of patients. Such testing is available clinically … Inherited in an autosomal recessive manner … Progressive microcephaly with loss of cognitive skills … recurrent sinopulmonary infections … Increased risk for cancer, particularly lymphoma … Microcephaly occurs in about 75% of patients at birth, and in the remainder of patients during the first months of life … Growth retardation may be present at birth or becomes manifest before two years of age … The characteristic facial features including a sloping forehead, receding mandible, prominent nasal root and nose, large ears, and upward slant of the palpebral fissures become apparent at around three years of age … Inversions and translocations involving chromosomes 7 and 14 are observed in PHA-stimulated lymphocytes in 10% to 50% of metaphases. The breakpoints most commonly involved are 7p13, 1q35, 14q11 and 14q32 … Molecular Genetic Testing … Mutation analysis of the NBS1 gene (chromosomal locus 89q21) and linkage analysis … Clinical Description … Growth … Lower than normal birth weight and small for gestational age … 25 of the 70 patients (35%) reported to date have developed malignancies between the ages of one and 34 years. Twenty-two of the 25 were lymphomas … High incidence of primary ovarian failure in both prepubertal girls and adolescent and post-adolescent women … elevated gonadotrophin … amenorrhea … lack of secondary sexual development … Phenotype in males is not yet clear … Irregular skin pigmentation, manifested as hyperpigmented or hypopigmented irregular spots, is seen in most patients. Congenital malformations, include hydrocephalus, preaxial polydactyly, occipital cyst, choanal atresia, cleft lip and palate, tracheal hypoplasia, horseshoe kidney, hydronephrosis, hypospadias, anal stenosis/atresia, and congenital hip dysplasia … There are no reliable estimates of prevalence … NBS is most common in East European/Slavic population … Studies in Poland, the Czech Republic, and Ukraine carrier frequency of the common allele approaches 1/155 in these populations.
NBS
April 29, 2003
[Italian]
La Nijmegen Breakage Syndrome (NBS) fu delineata nel 1981 da C. Weemaes
e colleghi (Nijmegen, Olanda), i quali osservarono una famiglia olandese con
genitori consanguinei e due figli affetti da microcefalia, ritardo di crescita,
anomalie cutanee, ritardo mentale e immunodeficienza; nelle colture linfocitarie
del paziente più giovane fu osservata un'elevata incidenza di riarrangiamenti
coinvolgenti i cromosomici 7 e 14. Da allora più di 130 casi sono stati
identificati in tutto il mondo e un Registro Internazionale della NBS è
attualmente tenuto a Nijmegen. Il gene NBS1 (le cui mutazioni bialleliche
causano la NBS) è stato identificato nel 1998.
Nijmegen Breakage Syndrome
Victor A. McKusick, OMIM, Johns Hopkins University, June 22, 2007
[for Professionals mainly]
Gene Map Locus: 8q21 … Weemaes et al. (1981) described 2 sons of second-cousin parents who had microcephaly, stunted growth, mental retardation, cafe-au-lait spots, and immunodeficiency … Chromosome instability with multiple rearrangement of chromosome 7 and 14 … Seemanova et al. (1985) described 9 patients in 6 families with a 'new' disorder characterized by low birth weight for date, microcephaly with normal intelligence, receding mandibula, cellular and humoral immune defects, and increased risk of lymphoreticular malignancies … Teebi et al. (1987) reported a large inbred Arab kindred in which 8 individuals in 5 sibships had microcephaly and normal intelligence. Two died of acute lymphoreticular malignancy or bronchial pneumonia … It is now quite clear that at least 1 of the patients of Weemaes et al. (1981) and at least 2 of the patients of Seemanova et al (1985) had the same basic defect … Ataxia-Telangiectasia variant-1 is the designation applied to the Nijmegen breakage syndrome and AT variant-2, the designation for the Berlin breakage syndrome (600885) … Despite the fact that these patients have neither ataxia nor telangiectasia, they historically have been categorized as AT variants.
Rare Birth Defect Linked to Cellular DNA Damage Response - Nijmegen Breakage Syndrome or NBS
Lynn Yarris, January 15, 1999
Berkeley Lab … (NBS) … Babies who appear normal at birth fail to develop normal size skulls (microcephaly) … Low IQs, variable immune deficiencies, and an extremely high incidence of cancer … Absence of a protein called "p95" is the cause of NBS.
Incidence of the major Nijmegen breakage syndrome (NBS) mutation 657del5 in Czech Republic, Poland and Ukraine
R. Varon, et. al … Institute of Human Genetics, Humboldt University, Charite, Berlin, Germany … We identified a total of 7 truncating mutations in different NBS patients, the majority being homozygous for mutation 657del5 in exon 6. We found this mutation in 68 unrelated NBS patients … We analyzed 1713 randomly selected, anonymous Guthrie cards from new-borns, 645 from Czech Republic, 568 from Poland and 500 from Ukraine … We now plan to access the exact cancer risk for these individuals through epidemiological studies.
Reports on the Rare Diseases and Conditions
Office of Rare Dieseases, National Institutes of Health
Nijmegen Breakage Syndrome Gene
Stylianos E. Antonarakis, OMIM, Johns Hopkins University, August 10, 2007
[for Professionals mainly]
Nibrin p95 Protein of the MRE11/RAD50 Complex. An autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition … hypersensitive to ionizing radiation with cytogenetic features indistinguishable from those of ataxia-telangiectasia … critical interval on chromosome 8q21 … gene encoding p95 …
ATM-dependent phosphorylation of nibrin
… mre11 complex and ATM … expression of the NBS1 gene … aberrant DNA structures … mapping of a mouse … Nijmegen breakage syndrome … Genes and cancer. NBS1 (Nijmegen breakage syndrome) … Chromosomal breakage syndromes … Radiation, DNA damage and cancer …
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Last Updated: 2008/1/07
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