PMID- 26681308
OWN - NLM
STAT- MEDLINE
DCOM- 20160518
LR  - 20231213
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 6
DP  - 2015 Dec 18
TI  - A novel Fanconi anaemia subtype associated with a dominant-negative mutation in 
      RAD51.
PG  - 8829
LID - 10.1038/ncomms9829 [doi]
LID - 8829
AB  - 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.
FAU - Ameziane, Najim
AU  - Ameziane N
AD  - Department of Clinical Genetics, VU University Medical Center, Van der 
      Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.
FAU - May, Patrick
AU  - May P
AD  - Luxembourg Centre for Systems Biomedicine, House of Biomedicine, 7 Avenue des 
      Hauts-Fourneaux, Esch/Alzette L-4362, Luxembourg.
AD  - Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 
      98109-5234, USA.
FAU - Haitjema, Anneke
AU  - Haitjema A
AD  - Department of Clinical Genetics, VU University Medical Center, Van der 
      Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.
FAU - van de Vrugt, Henri J
AU  - van de Vrugt HJ
AD  - Department of Clinical Genetics, VU University Medical Center, Van der 
      Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.
AD  - Division of Biological Stress Response, The Netherlands Cancer Institute, 
      Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands.
FAU - van Rossum-Fikkert, Sari E
AU  - van Rossum-Fikkert SE
AD  - Department of Genetics, Cancer Genomics Center, PO Box 2040, Rotterdam 3000 CA, 
      The Netherlands.
AD  - Department of Radiation Oncology, Erasmus Medical Center, PO Box 2040, Rotterdam 
      3000 CA, The Netherlands.
FAU - Ristic, Dejan
AU  - Ristic D
AD  - Department of Genetics, Cancer Genomics Center, PO Box 2040, Rotterdam 3000 CA, 
      The Netherlands.
AD  - Department of Radiation Oncology, Erasmus Medical Center, PO Box 2040, Rotterdam 
      3000 CA, The Netherlands.
FAU - Williams, Gareth J
AU  - Williams GJ
AD  - Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, California 
      94720, USA.
FAU - Balk, Jesper
AU  - Balk J
AD  - Department of Clinical Genetics, VU University Medical Center, Van der 
      Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.
FAU - Rockx, Davy
AU  - Rockx D
AD  - Department of Clinical Genetics, VU University Medical Center, Van der 
      Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.
FAU - Li, Hong
AU  - Li H
AD  - Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 
      98109-5234, USA.
FAU - Rooimans, Martin A
AU  - Rooimans MA
AD  - Department of Clinical Genetics, VU University Medical Center, Van der 
      Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.
FAU - Oostra, Anneke B
AU  - Oostra AB
AD  - Department of Clinical Genetics, VU University Medical Center, Van der 
      Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.
FAU - Velleuer, Eunike
AU  - Velleuer E
AD  - 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.
FAU - Dietrich, Ralf
AU  - Dietrich R
AD  - Deutsche Fanconi-Anamie-Hilfe e.V., Bockenweg 4, 59427 Unna, Germany.
FAU - Bleijerveld, Onno B
AU  - Bleijerveld OB
AD  - Mass Spectrometry and Proteomics Facility, The Netherlands Cancer Institute, 
      Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands.
FAU - Maarten Altelaar, A F
AU  - Maarten Altelaar AF
AD  - Mass Spectrometry and Proteomics Facility, The Netherlands Cancer Institute, 
      Plesmanlaan 121, Amsterdam 1066 CX, The Netherlands.
FAU - Meijers-Heijboer, Hanne
AU  - Meijers-Heijboer H
AD  - Department of Clinical Genetics, VU University Medical Center, Van der 
      Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.
FAU - Joenje, Hans
AU  - Joenje H
AD  - Department of Clinical Genetics, VU University Medical Center, Van der 
      Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.
FAU - Glusman, Gustavo
AU  - Glusman G
AD  - Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 
      98109-5234, USA.
FAU - Roach, Jared
AU  - Roach J
AD  - Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 
      98109-5234, USA.
FAU - Hood, Leroy
AU  - Hood L
AD  - Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 
      98109-5234, USA.
FAU - Galas, David
AU  - Galas D
AD  - Luxembourg Centre for Systems Biomedicine, House of Biomedicine, 7 Avenue des 
      Hauts-Fourneaux, Esch/Alzette L-4362, Luxembourg.
AD  - Pacific Northwest Diabetes Research Institute, 720 Broadway, Seattle, Washington 
      98122, USA.
FAU - Wyman, Claire
AU  - Wyman C
AD  - Department of Genetics, Cancer Genomics Center, PO Box 2040, Rotterdam 3000 CA, 
      The Netherlands.
AD  - Department of Radiation Oncology, Erasmus Medical Center, PO Box 2040, Rotterdam 
      3000 CA, The Netherlands.
FAU - Balling, Rudi
AU  - Balling R
AD  - Luxembourg Centre for Systems Biomedicine, House of Biomedicine, 7 Avenue des 
      Hauts-Fourneaux, Esch/Alzette L-4362, Luxembourg.
FAU - den Dunnen, Johan
AU  - den Dunnen J
AD  - Department of Human and Clinical Genetics, Leiden University Medical Center, 
      Albinusdreef 2, Leiden 2333ZA, The Netherlands.
FAU - de Winter, Johan P
AU  - de Winter JP
AD  - Department of Clinical Genetics, VU University Medical Center, Van der 
      Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.
FAU - Kanaar, Roland
AU  - Kanaar R
AD  - Department of Genetics, Cancer Genomics Center, PO Box 2040, Rotterdam 3000 CA, 
      The Netherlands.
AD  - Department of Radiation Oncology, Erasmus Medical Center, PO Box 2040, Rotterdam 
      3000 CA, The Netherlands.
FAU - Gelinas, Richard
AU  - Gelinas R
AD  - Institute for Systems Biology, 401 Terry Avenue North, Seattle, Washington 
      98109-5234, USA.
FAU - Dorsman, Josephine C
AU  - Dorsman JC
AD  - Department of Clinical Genetics, VU University Medical Center, Van der 
      Boechorststraat 7, Amsterdam 1081 BT, The Netherlands.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151218
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (DNA-Binding Proteins)
RN  - EC 3.6.- (Acid Anhydride Hydrolases)
RN  - EC 3.6.- (RAD50 protein, human)
RN  - EC 6.5.1.- (DNA Repair Enzymes)
SB  - IM
MH  - Acid Anhydride Hydrolases
MH  - Base Sequence
MH  - DNA Damage
MH  - DNA Repair
MH  - DNA Repair Enzymes/*genetics/metabolism
MH  - DNA-Binding Proteins/*genetics/metabolism
MH  - Fanconi Anemia/*enzymology/genetics
MH  - Humans
MH  - Male
MH  - Molecular Sequence Data
MH  - *Mutation, Missense
MH  - Recombination, Genetic
MH  - Young Adult
PMC - PMC4703882
EDAT- 2015/12/19 06:00
MHDA- 2016/05/19 06:00
PMCR- 2016/01/07
CRDT- 2015/12/19 06:00
PHST- 2015/05/27 00:00 [received]
PHST- 2015/10/07 00:00 [accepted]
PHST- 2015/12/19 06:00 [entrez]
PHST- 2015/12/19 06:00 [pubmed]
PHST- 2016/05/19 06:00 [medline]
PHST- 2016/01/07 00:00 [pmc-release]
AID - ncomms9829 [pii]
AID - 10.1038/ncomms9829 [doi]
PST - epublish
SO  - Nat Commun. 2015 Dec 18;6:8829. doi: 10.1038/ncomms9829.