A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51.

Autor: Ameziane N; Department of Clinical Genetics, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands., May P; Luxembourg Centre for Systems Biomedicine, House of Biomedicine, 7 Avenue des Hauts-Fourneaux, Esch/Alzette L-4362, Luxembourg.; Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109-5234, USA., Haitjema A; Department of Clinical Genetics, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands., van de Vrugt HJ; Department of Clinical Genetics, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.; Division of Biological Stress Response, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands., van Rossum-Fikkert SE; Department of Genetics, Cancer Genomics Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands.; Department of Radiation Oncology, Erasmus Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands., Ristic D; Department of Genetics, Cancer Genomics Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands.; Department of Radiation Oncology, Erasmus Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands., Williams GJ; Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 94720, USA., Balk J; Department of Clinical Genetics, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands., Rockx D; Department of Clinical Genetics, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands., Li H; Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109-5234, USA., Rooimans MA; Department of Clinical Genetics, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands., Oostra AB; Department of Clinical Genetics, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands., Velleuer E; Department of Paediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health, Medical Faculty, Heinrich Heine University, Moorenstrasse 5, 40225 Du¨sseldorf, Germany., Dietrich R; Deutsche Fanconi-Anämie-Hilfe e.V., Böckenweg 4, 59427 Unna, Germany., Bleijerveld OB; Mass Spectrometry and Proteomics Facility, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands., Maarten Altelaar AF; Mass Spectrometry and Proteomics Facility, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands., Meijers-Heijboer H; Department of Clinical Genetics, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands., Joenje H; Department of Clinical Genetics, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands., Glusman G; Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109-5234, USA., Roach J; Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109-5234, USA., Hood L; Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109-5234, USA., Galas D; Luxembourg Centre for Systems Biomedicine, House of Biomedicine, 7 Avenue des Hauts-Fourneaux, Esch/Alzette L-4362, Luxembourg.; Pacific Northwest Diabetes Research Institute, 720 Broadway, Seattle, Washington 98122, USA., Wyman C; Department of Genetics, Cancer Genomics Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands.; Department of Radiation Oncology, Erasmus Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands., Balling R; Luxembourg Centre for Systems Biomedicine, House of Biomedicine, 7 Avenue des Hauts-Fourneaux, Esch/Alzette L-4362, Luxembourg., den Dunnen J; Department of Human and Clinical Genetics, Leiden University Medical Center, Albinusdreef 2, Leiden 2333ZA, The Netherlands., de Winter JP; Department of Clinical Genetics, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands., Kanaar R; Department of Genetics, Cancer Genomics Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands.; Department of Radiation Oncology, Erasmus Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands., Gelinas R; Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 98109-5234, USA., Dorsman JC; Department of Clinical Genetics, VU University Medical Center, Van der Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2015 Dec 18; Vol. 6, pp. 8829. Date of Electronic Publication: 2015 Dec 18.
DOI: 10.1038/ncomms9829
Abstrakt: Fanconi anaemia (FA) is a hereditary disease featuring hypersensitivity to DNA cross-linker-induced chromosomal instability in association with developmental abnormalities, bone marrow failure and a strong predisposition to cancer. A total of 17 FA disease genes have been reported, all of which act in a recessive mode of inheritance. Here we report on a de novo g.41022153G>A; p.Ala293Thr (NM_002875) missense mutation in one allele of the homologous recombination DNA repair gene RAD51 in an FA-like patient. This heterozygous mutation causes a novel FA subtype, 'FA-R', which appears to be the first subtype of FA caused by a dominant-negative mutation. The patient, who features microcephaly and mental retardation, has reached adulthood without the typical bone marrow failure and paediatric cancers. Together with the recent reports on RAD51-associated congenital mirror movement disorders, our results point to an important role for RAD51-mediated homologous recombination in neurodevelopment, in addition to DNA repair and cancer susceptibility.
Databáze: MEDLINE
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