A collection of disease information resources and questions answered by our genetic and rare diseases information specialists for nijmegen breakage. Forgotten diseases research foundation nijmegen breakage. Nibrin, the product of the nbn gene, is part of the mre11rad50 mrn complex that is involved in the repair of dna double strand breaks dsbs, and plays a critical role in the. Nijmegen breakage syndrome nbs mim 251260 is a rare autosomal recessive disorder, characterized by microcephaly, facial dysmorphism, growth retardation, immunodeficiency, hypersensitivity to ionizing radiation ir and a highly increased risk for lymphoreticular malignancy. Complementation studies of different nbs cell lines suggested genetic heterogeneity and two groups were distinguished. Nijmegen breakage syndrome nijmegen breakage syndrome nbs is one of the rarest genetic disorders, it is an autosomal recessive disease and its defective gene nbs1 is located on chromosome 8q21. Mutations in the nbn nbs1 gene located in band 8q21 ar. The syndrome is most common in eastern europe due to a slavic founder mu. The disease seems to be more prevalent among central and eastern european populations, with polish patients constituting approximately half of all registered nbs patients worldwide.
Rad50 deficiency appears to be extremely rare, with only a single case reported in the literature 20. The international nijmegen breakage syndrome study group. Nijmegen breakage syndrome neurodegenerative diseases edit chromosome instability syndromes include several inherited neurodegenerative diseases that are due to mutations in genes that encode enzymes necessary for dna repair. Nijmegen breakage syndrome nbs is a rare autosomal recessive dna repair disorder characterized by microcephaly, immunodeficiency and cancer 1, 2. Nijmegen breakage syndrome nbs, a rare autosomal recessive condition also known as ataxia telangiectasia at variants v1 and v2, is characterised by. A variant of the nijmegen breakage syndrome with unusual. Nijmegen breakage syndrome nbs is an autosomal recessive disorder characterized by small head size, distinctive facial features, intellectual disability, short stature, immunodeficiency, and cancer predisposition 1. Nijmegen breakage syndrome genetic and rare diseases. Nijmegen breakage syndrome nbs is a relatively rare chromosomal instability disorder with an estimated incidence of less than 1. Functional deficiency of nbn, the nijmegen breakage. Neonatal screening for severe primary immunodeficiency.
The nijmegen breakage syndrome protein is essential for mre11 phosphorylation upon dna damage. Children with the syndrome appear abnormal with stunted growth before and after birth, small head, large ears, long nose, cleft lip or palate, small chin, and cafe au lait. Get a printable copy pdf file of the complete article 1. Nijmegen breakage syndrome cells fail to induce the p53mediated dna damage response following exposure to ionizing radiation.
Nijmegen breakage syndrome is a condition characterized by short stature, an unusually small head size microcephaly, distinctive facial features, recurrent respiratory tract infections, an increased risk of cancer, intellectual disability, and other health problems people with this condition typically grow slowly during infancy and early childhood. The patient was initially diagnosed with nbs, given her clinical features of microcephaly, characteristic facial features, skin pigmentation abnormalities and short stature. Abstractwe report on pediatric patient with nijmegen breakage syndrome nbs, a rare dna repair. Nijmegen breakage syndrome caused by nbs1 germline mutations is a rare autosomal recessive disease with clinical features that include microcephaly. Nijmegen breakage syndrome genetics home reference nih. Mutation inactivation of nijmegen breakage syndrome gene. Nijmegen breakage syndrome, cell line, unbalanced translocation, proliferative advantage background nijmegen breakage syndrome nbs is an autosomal recessive disorder characterized by chromosome instability associated with microcephaly, immunodeficiency, hypersensitivity to xirradiation, and a high predisposition to cancer.
An adult patient with nijmegen breakage syndrome and. Nijmegen breakage syndrome nbs is a rare autosomal recessive dna repair disorder characterized by immune deficiency, microcephaly, mental retardation and a disposition for the development of hematological malignancies. Nijmegen breakage syndrome and chronic polyarthritis. It has many other names such as at variant 1, at variant 2, berlin breakage syndrome, czech breakage syndrome, and seemanova syndrome. With no know cure and few treatment options aimed at only a subset of its side effects, research surrounding nbs is in need of expansion. Nijmegen breakage syndrome is a rare genetic disease presenting at birth with microcephaly, dysmorphic facial features, becoming more noticeable with age, growth delay, and lateronset complications such as malignancies and infections. Mutant murine models of nijmegen breakage syndrome have been derived. Nijmegen breakage syndrome nbs is a rare autosomal recessive disorder characterized by microcephaly, immunodeficiency, and predisposition to hematopoietic malignancy.
It was very painful for her and the first diagnosis was a boil. Clinical presentation microcephaly present at birth and progressive with age dysmorp. Fibroblastderived integrationfree ipsc line isrmnbs1. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a pdf plugin installed and enabled in your browser. Nijmegen breakage syndrome nbs is a rare autosomal recessive syndrome of chromosomal instability mainly characterized by microcephaly at birth, combined immunodeficiency and predisposition to malignancies. At variant 1 atv1 or nijmegen breakage syndrome and at variant 2 atv2 or berlin breakage syndrome 5, 8. Mutations in the nbn nbs1 gene located in band 8q21 are responsible for. We aimed to investigate its functional impact in breast. Nijmegen breakage syndrome nbs is a rare autosomal recessive condition of chromosomal instability that is clinically characterized by microcephaly, a distinct facial appearance, short stature, immunodeficiency, radiation sensitivity, and a strong predisposition to lymphoid malignancy. Research article open access functional deficiency of. Nijmegen breakage syndrome nbs is a rare autosomal recessive. Mutation inactivation of nijmegen breakage syndrome gene nbs1 in hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Nijmegen breakage syndrome nbs is a rare autosomal recessive dna repair disorder characterized by a 5 bp deletion in the nbs1 gene on chromosome 8q21, which leads to a truncated and insufficiently functioning protein nibrin.
Pdf nijmegen breakage syndrome krystyna chrzanowska. Mutational inactivation of the nijmegen breakage syndrome. When my daughter was 7yrs old a lump appeared near her anus. Pdf nijmegen breakage syndrome nbs is a rare autosomal recessive condition with chromosomal instability. So far, mostly pediatric patients have been described, since the underlying condition is often fatal before adulthood. Nbs is due to hypomorphic mutations of nbs1 gene, encoding less functional nibrin, a protein involved in the repair of dna doublestrand breaks and in cell cycle checkpoints. This website uses cookies to ensure you get the best experience on our website. About half of individuals with nijmegen breakage syndrome develop non hodgkin lymphoma, usually before age 15. Clinical and routine laboratory information of the recruited patients with ataxia telangiectasia or nijmegen breakage syndrome pdf, 24. A murine model of nijmegen breakage syndrome sciencedirect. In a patient with a nijmegen breakage syndromelike disorder nbsld, waltes et al. R215w missense mutation occurs at subpolymorphic frequencies in several populations. Jongmans w, vuillaume m, chrzanowska k, smeets d, sperling k, hall j molecular and cellular biology. The gene product, nibrin, is a novel protein, which is member of the hmre11hrad50 protein complex, suggesting that the gene is involved in dna double strand break repair.
Clinical and immunological features, longterm outcome and treatment options a retrospective analysis. Nijmegen breakage syndrome is a rare genetic disease presenting at. Mutations in nbn, the gene for nijmegen breakage syndrome nbs, are thought to predispose women to developing breast cancer, but a breast cancer cell line containing mutations in nbn has not yet been described. Absence of nibrin protein nbs1 gene, part of mrn complex involved in dna doublestrand break recognition and repair.
Nijmegen breakage syndrome radiology reference article. Due to a founder mutation in the underlying nbn gene c. Clinical manifestation of nijmegen breakage syndrome. Human fibroblasts cells from a female diagnosed with nijmegen breakage syndrome nbs carrying the homozygous nbn c. The nijmegen breakage syndrome and the phenotypically indistinguishable berlin breakage syndrome are autosomal recessive chromosomal instability syndromes characterized by microcephaly, growth retardation, immunodeficiency, and predisposition to cancer. The gene mutated in nbs has been identified and it was. The clinical and cellular phenotypes of nbs substantially overlap those of ataxiatelangiectasia at. Nijmegen breakage syndrome is a devastating disorder in which the affected children suffer from pronounced microcephaly, cognitive impairments, dwarfism, strong cancer predisposition, and. Introduction nijmegen breakage syndrome, a rare disease of chromosomal instability, is a life altering disorder. My daughter has nijmegen breakage syndrome rare disease day. I took emma back to the hospital as she could barely sit down and this time i was told it was. Nijmegen breakage syndromelike disorder rad50 deficiency. Nijmegen breakage syndrome nbs is a rare autosomal recessive syndrome of chromosomal instability mainly characterized by microcephaly at birth, combined immunodeficiency and predisposition to. Nbs1, the gene defective in nbs, is located on chromosome 8q21 and has recently been cloned.
Pdf differentiation of nijmegen breakage syndrome from fanconi. Nijmegen breakage syndromelike disorder dna repair chapter low levels of unstable rad50 protein. Background nijmegen breakage syndrome nbs is a rare autosomal recessive disorder. Pdf nijmegen breakage syndrome nbs is a rare autosomal recessive syndrome of chromosomal instability mainly characterized by microcephaly at birth. Nijmegen breakage syndrome nbs, is a rare autosomal recessive congenital disorder causing chromosomal instability, probably as a result of a defect in the double holliday junction dna repair mechanism andor the synthesis dependent strand annealing mechanism for repairing double strand breaks in dna see homologous recombination nbs1 codes for a protein that.
Nijmegen breakage syndrome genetic and rare diseases nih. A genetic disease named for the city of nijmegen in the netherlands with increased chromosome breakage, immunodeficiency and an increased risk of malignancy. Nijmegen breakage syndrome nbs, a rare autosomal recessive condition also known as ataxia telangiectasia at variants v1 and v2, is characterised by microcephaly, typical facies, short stature, immunodeficiency, and chromosomal instability. Nbs is an autosomal recessive chromosomal instability disorder characterised by microcephaly, stunted growth, immunodeficiency, a high cancer predisposition and a marked sensitivity towards ionising radiation 7. Nijmegen breakage syndrome archives of disease in childhood. Evidence for a premalignant cell line in a skin biopsy.
Nijmegen breakage syndrome is a rare genetic disease presenting at birth. Nijmegen breakage syndrome nbs orphanet journal of. This article is from italian journal of pediatrics, volume 39. Nijmegen breakage syndrome is an autosomal recessive disease caused by mutations in the nbn gene. By mediating the phospho atmdriven assembly of brca, mre11 and rad50 on double strand breaks, nibrin carries a central. Nijmegen breakage syndrome is an autosomal recessive disorder characterized by microcephaly, immunodeficiency, hypersensitivity to xirradiation, and a high predisposition to cancer. Nijmegen breakage syndrome nbs orphanet journal of rare. Backgroundnijmegen breakage syndrome nbs is a rare autosomal recessive disorder. Carrier screening to help detect the risk of having a baby with a specific inherited disorder, such as cystic fibrosis. Nijmegen breakage syndrome is a condition characterized by short stature, an unusually small head size microcephaly, distinctive facial features, recurrent respiratory tract infections, an increased risk of cancer, intellectual disability, and other health problems.
Nijmegen breakage syndrome, also known as seemanova syndrome or berlin breakage syndrome, is a rare autosomal recessive syndrome of chromosomal instability. Nbs1, the gene defective in nbs, is located on chromosome 8q21. Wolskakusnierz b, gregorek h, chrzanowska k, et al. The nijmegen breakage syndrome and the phenotypically indistinguishable berlin. The photograph and charts were kindly provided by professor eva seemanova. Nijmegen breakage syndrome nbs is characterized by progressive microcephaly, intrauterine growth retardation and short stature, recurrent sinopulmonary infections, an increased risk for cancer, and premature ovarian failure in females. Tlymphoblastic leukemialymphoma in macedonian patients. Radiation oncologycancer syndromesnijmegen breakage.