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          Institute: MPI für molekulare Genetik     Collection: Research Group Development and Disease     Display Documents



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ID: 539705.0, MPI für molekulare Genetik / Research Group Development and Disease
Clinical variability and novel mutations in the NHEJ1 gene in patients with a Nijmegen breakage syndrome-like phenotype.
Authors:Dutrannoy, V.; Demuth, I.; Baumann, U.; Schindler, D.; Konrat, K.; Neitzel, H.; Gillessen-Kaesbach, G.; Radszewski, J.; Rothe, S.; Schellenberger, M. T.; Nurnberg, G.; Nurnberg, P.; Teik, K. W.; Nallusamy, R.; Reis, A.; Sperling, K.; Digweed, M.; Varon, R.
Language:English
Date of Publication (YYYY-MM-DD):2010-07-01
Title of Journal:Human Mutation
Journal Abbrev.:Hum Mutat
Volume:31
Issue / Number:9
Start Page:1059
End Page:1068
Copyright:© 2010 Wiley-Liss, Inc.
Review Status:not specified
Audience:Experts Only
Abstract / Description: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 recently, a new member of the NHEJ repair pathway, NHEJ1, was discovered, and mutations in patients with features resembling NBS were described. Here we report on five patients from four families of different ethnic origin with the NBS-like phenotype. Sequence analysis of the NHEJ1 gene in a patient of Spanish and in a patient of Turkish origin identified homozygous, previously reported mutations, c.168C>G (p.Arg57Gly) and c.532C>T (p.Arg178Ter), respectively. Two novel, paternally inherited truncating mutations, c.495dupA (p.Asp166ArgfsTer20) and c.526C>T (p.Arg176Ter) and two novel, maternal genomic deletions of 1.9 and 6.9 kb of the NHEJ1 gene, were found in a compound heterozygous state in two siblings of German origin and in one Malaysian patient, respectively. Our findings confirm that patients with NBS-like phenotypes may have mutations in the NHEJ1 gene including multiexon deletions, and show that considerable clinical variability could be observed even within the same family.
Free Keywords:Nijmegen Breakage Syndrome-like;
NBS;
microcephaly;
NHEJ1 gene;
clinical variability
Comment of the Author/Creator:Correspondence: Raymonda Varon, Institute of Human Genetics, Charitá, Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany
External Publication Status:published
Document Type:Article
Communicated by:Stefan Mundlos
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Institute of Human Genetics, Charitè Universitätsmedizin, Berlin, Germany;
2.Department of Pediatric Pulmonology and Neonatology, Medical School Hannover, Hannover, Germany;
3.Department of Human Genetics, University of Würzburg, Würzburg, Germany;
4.Institute of Human Genetics, Universität zu Lübeck; Lübeck, Germany;
5.Cologne Center for Genomics and Institute for Genetics, University of Cologne, Cologne, Germany;
6.Hospital Pulau Pinang, Jalan Residensi, Malays;
7.Institute of Human Genetics, University Hospital Erlangen, Friedrich–Alexander University Erlangen–Nuremberg, Erlangen, Germany;
8.Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
Identifiers:ISSN:1059-7794 [ID No:1]
URL:http://www.ncbi.nlm.nih.gov/pubmed/20597108 [ID No:2]
DOI:10.1002/humu.21315 [ID No:3]
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