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

Najim Ameziane; Patrick May; Anneke Haitjema; Henri J. van de Vrugt; Sari E. van Rossum-Fikkert; Dejan Ristic; Gareth J. Williams; Jesper Balk; Davy Rockx; Hong Li; Martin A. Rooimans; Anneke B. Oostra; Eunike Velleuer; Ralf Dietrich; Onno B. Bleijerveld; A. F. Maarten Altelaar; Hanne Meijers-Heijboer; Hans Joenje; Gustavo Glusman; Jared Roach; Leroy Hood; David Galas; Claire Wyman; Rudi Balling; Johan den Dunnen; Johan P. de Winter; Roland Kanaar; Richard Gelinas; Josephine C. Dorsman

doi:https://doi.org/10.1038/ncomms9829

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

Najim Ameziane, Patrick May, Anneke Haitjema, Henri J. van de Vrugt, Sari E. van Rossum-Fikkert, Dejan Ristic, Gareth J. Williams, Jesper Balk, Davy Rockx, Hong Li, Martin A. Rooimans, Anneke B. Oostra, Eunike Velleuer, Ralf Dietrich, Onno B. Bleijerveld, A. F. Maarten Altelaar, Hanne Meijers-Heijboer, Hans Joenje, Gustavo Glusman, Jared RoachLeroy Hood, David Galas, Claire Wyman, Rudi Balling, Johan den Dunnen, Johan P. de Winter, Roland Kanaar, Richard Gelinas, Josephine C. Dorsman

Research output: Contribution to journal › Article › Academic › peer-review

107 Citations (Scopus)

Abstract

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

Original language	English
Article number	8829
Pages (from-to)	8829
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms9829
Publication status	Published - 2015

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https://doi.org/10.1038/ncomms9829

Cite this

Ameziane, N., May, P., Haitjema, A., van de Vrugt, H. J., van Rossum-Fikkert, S. E., Ristic, D., Williams, G. J., Balk, J., Rockx, D., Li, H., Rooimans, M. A., Oostra, A. B., Velleuer, E., Dietrich, R., Bleijerveld, O. B., Maarten Altelaar, A. F., Meijers-Heijboer, H., Joenje, H., Glusman, G., ... Dorsman, J. C. (2015). A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51. Nature communications, 6, 8829. Article 8829. https://doi.org/10.1038/ncomms9829

@article{a6f7f3e39c9b48699d93df6e622ab7a0,

title = "A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51",

abstract = "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",

author = "Najim Ameziane and Patrick May and Anneke Haitjema and {van de Vrugt}, {Henri J.} and {van Rossum-Fikkert}, {Sari E.} and Dejan Ristic and Williams, {Gareth J.} and Jesper Balk and Davy Rockx and Hong Li and Rooimans, {Martin A.} and Oostra, {Anneke B.} and Eunike Velleuer and Ralf Dietrich and Bleijerveld, {Onno B.} and {Maarten Altelaar}, {A. F.} and Hanne Meijers-Heijboer and Hans Joenje and Gustavo Glusman and Jared Roach and Leroy Hood and David Galas and Claire Wyman and Rudi Balling and {den Dunnen}, Johan and {de Winter}, {Johan P.} and Roland Kanaar and Richard Gelinas and Dorsman, {Josephine C.}",

year = "2015",

doi = "https://doi.org/10.1038/ncomms9829",

language = "English",

volume = "6",

pages = "8829",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

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Ameziane, N, May, P, Haitjema, A, van de Vrugt, HJ, van Rossum-Fikkert, SE, Ristic, D, Williams, GJ, Balk, J, Rockx, D, Li, H, Rooimans, MA, Oostra, AB, Velleuer, E, Dietrich, R, Bleijerveld, OB, Maarten Altelaar, AF, Meijers-Heijboer, H , Joenje, H, Glusman, G, Roach, J, Hood, L, Galas, D, Wyman, C, Balling, R, den Dunnen, J, de Winter, JP, Kanaar, R, Gelinas, R & Dorsman, JC 2015, 'A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51', Nature communications, vol. 6, 8829, pp. 8829. https://doi.org/10.1038/ncomms9829

TY - JOUR

T1 - A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51

AU - Ameziane, Najim

AU - May, Patrick

AU - Haitjema, Anneke

AU - van de Vrugt, Henri J.

AU - van Rossum-Fikkert, Sari E.

AU - Ristic, Dejan

AU - Williams, Gareth J.

AU - Balk, Jesper

AU - Rockx, Davy

AU - Li, Hong

AU - Rooimans, Martin A.

AU - Oostra, Anneke B.

AU - Velleuer, Eunike

AU - Dietrich, Ralf

AU - Bleijerveld, Onno B.

AU - Maarten Altelaar, A. F.

AU - Meijers-Heijboer, Hanne

AU - Joenje, Hans

AU - Glusman, Gustavo

AU - Roach, Jared

AU - Hood, Leroy

AU - Galas, David

AU - Wyman, Claire

AU - Balling, Rudi

AU - den Dunnen, Johan

AU - de Winter, Johan P.

AU - Kanaar, Roland

AU - Gelinas, Richard

AU - Dorsman, Josephine C.

PY - 2015

Y1 - 2015

N2 - 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

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

U2 - https://doi.org/10.1038/ncomms9829

DO - https://doi.org/10.1038/ncomms9829

M3 - Article

C2 - 26681308

SN - 2041-1723

VL - 6

SP - 8829

JO - Nature communications

JF - Nature communications

M1 - 8829

ER -