𝔖 Bobbio Scriptorium
✦   LIBER   ✦

Nijmegen Breakage Syndrome mutations and risk of breast cancer

✍ Scribed by Natalia Bogdanova; Sergei Feshchenko; Peter Schürmann; Regina Waltes; Britta Wieland; Peter Hillemanns; Yuri I. Rogov; Olaf Dammann; Michael Bremer; Johann H. Karstens; Christof Sohn; Raymonda Varon; Thilo Dörk

Publisher
John Wiley and Sons
Year
2007
Tongue
French
Weight
125 KB
Volume
122
Category
Article
ISSN
0020-7136

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

Mutations in the NBS1 gene have been identified as disease‐causing mutations in patients with Nijmegen Breakage Syndrome (NBS), but their clinical impact on breast cancer susceptibility has remained uncertain. We determined the frequency of 2 NBS mutations, 657del5 and R215W, in two large series of breast cancer cases and controls from Northern Germany and from the Republic of Belarus. The 5‐bp‐deletion 657del5 was identified in 15/1,588 cases (0.9%) from Belarus and in 1/1,076 cases (0.1%) from Germany but in only 1/1,014 population controls from Belarus and 0/1017 German controls (p < 0.01). The missense substitution R215W was observed in 9/1,588 Byelorussian and 9/1,076 German patients (0.6% and 0.8%, respectively) but was also present in 5/1,014 Byelorussian and 2/1,017 German control individuals (adjusted OR = 1.9, 95%CI 0.8–4.6, p = 0.18). Studies of lymphoblastoid cell lines revealed that NBS1/p95 protein levels were reduced to 70% in cells from a heterozygous breast cancer patient carrying R215W and to 15% in cells from a NBS patient compound heterozygous for 657del5/R215W suggesting that the R215W substitution may be associated with protein instability. Levels of radiation‐induced phosphorylation of Nbs1/p95(Ser343) were reduced to 60% and 35% of wildtype, respectively. Neither age at diagnosis nor family history of breast cancer differed significantly between carriers and noncarriers of NBS mutations. The combined data are in line with an about 3‐fold increase in breast cancer risk for female NBS heterozygotes (OR 3.1; 95%CI 1.4–6.6) and indicate that the 657del5 deletion and perhaps the R215W substitution contribute to inherited breast cancer susceptibility in Central and Eastern Europe. © 2007 Wiley‐Liss, Inc.

📜 SIMILAR VOLUMES

Possible new variant of Nijmegen breakag
Possible new variant of Nijmegen breakage syndrome
✍ Der Kaloustian, Vazken M.; Kleijer, Wim; Booth, Ann; Auerbach, Arleen D.; Mazer, 📂 Article 📅 1996 🏛 John Wiley and Sons 🌐 English ⚖ 611 KB

W e report on a child with microcephaly, small facial and body size, and immune deficiency. The phenotype is consistent with Nijmegen breakage syndrome (NBS), with additional clinical manifestations and laboratory findings not reported heretofore. Most investigations, including the results of radiat

Further delineation of the Nijmegen brea
Further delineation of the Nijmegen breakage syndrome
✍ Taalman, Rob D. F. M. ;Hustinx, Theo W. J. ;Weemaes, Corry M. R. ;Seemanová, Eva 📂 Article 📅 1989 🏛 John Wiley and Sons 🌐 English ⚖ 687 KB

We report on five independent families with a chromosome instability disorder that earlier had been called the Nijmegen breakage syndrome (NBS). These families, two from the Netherlands and three from Czechoslovakia, had a total of eight patients, five of whom are still alive. The main clinical mani

A patient with mutations in DNA Ligase I
A patient with mutations in DNA Ligase IV: Clinical features and overlap with Nijmegen breakage syndrome
✍ Tawfeg I. Ben-Omran; Karen Cerosaletti; Patrick Concannon; Sheila Weitzman; Marj 📂 Article 📅 2005 🏛 John Wiley and Sons 🌐 English ⚖ 111 KB 👁 1 views

## Abstract The clinical phenotype of Ligase IV syndrome (LIG4 syndrome), an extremely rare autosomal recessive condition caused by mutations in the __LIG4__ gene, closely resembles that of Nijmegen breakage syndrome (NBS), and is characterized by microcephaly, characteristic facial features, growt

Nijmegen breakage syndrome: consequences
Nijmegen breakage syndrome: consequences of defective DNA double strand break repair
✍ Martin Digweed; André Reis; Karl Sperling 📂 Article 📅 1999 🏛 John Wiley and Sons 🌐 English ⚖ 85 KB

The autosomal recessive genetic disorder, Nijmegen Breakage Syndrome, is characterised by an excessively high risk for the development of lymphatic tumours and an extreme sensitivity towards ionising radiation. The most likely explanation for these characteristics, a deficiency in the repair of DNA

Clinical variability and novel mutations
Clinical variability and novel mutations in the NHEJ1 gene in patients with a Nijmegen breakage syndrome-like phenotype
✍ Véronique Dutrannoy; Ilja Demuth; Ulrich Baumann; Detlev Schindler; Kateryna Kon 📂 Article 📅 2010 🏛 John Wiley and Sons 🌐 English ⚖ 463 KB

We have previously shown that mutations in the genes encoding DNA Ligase IV (LIGIV) and RAD50, involved in DNA repair by nonhomologous-end joining (NHEJ) and homologous recombination, respectively, lead to clinical and cellular features similar to those of Nijmegen Breakage Syndrome (NBS). Very rece