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

N Ameziane; P May; A Haitjema; HJ van de Vrugt; SE van Rossum-Fikkert; D. Ristic; GJ Williams; J Balk; D Rockx; H Li; MA Rooimans; AB Oostra; E Velleuer; R Dietrich; OB (Onno) Bleijerveld; AFM Altelaar; H Meijers-Heijboer; H Joenje; G Glusman; J Roach; L Hood; D Galas; C.L. Wyman; R Balling; J den Dunnen; JP (Johan) de Winter; Roland Kanaar; R Gelinas; JC Dorsman

doi:10.1038/ncomms9829

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

N Ameziane, P May, A Haitjema, HJ van de Vrugt, SE van Rossum-Fikkert, D. Ristic, GJ Williams, J Balk, D Rockx, H Li, MA Rooimans, AB Oostra, E Velleuer, R Dietrich, OB (Onno) Bleijerveld, AFM Altelaar, H Meijers-Heijboer, H Joenje, G Glusman, J RoachL Hood, D Galas, C.L. Wyman, R Balling, J den Dunnen, JP (Johan) de Winter, Roland Kanaar, R Gelinas, JC Dorsman

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

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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	Undefined/Unknown
Journal	Nature Communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms9829
Publication status	Published - 2015

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10.1038/ncomms9829

http://hdl.handle.net/1765/79468

Cite this

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., Altelaar, AFM., Meijers-Heijboer, H., Joenje, H., Glusman, G., ... Dorsman, JC. (2015). A novel Fanconi anaemia subtype associated with a dominant-negative mutation in RAD51. Nature Communications, 6. https://doi.org/10.1038/ncomms9829

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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 = "N Ameziane and P May and A Haitjema and {van de Vrugt}, HJ and {van Rossum-Fikkert}, SE and D. Ristic and GJ Williams and J Balk and D Rockx and H Li and MA Rooimans and AB Oostra and E Velleuer and R Dietrich and Bleijerveld, {OB (Onno)} and AFM Altelaar and H Meijers-Heijboer and H Joenje and G Glusman and J Roach and L Hood and D Galas and C.L. Wyman and R Balling and {den Dunnen}, J and {de Winter}, {JP (Johan)} and Roland Kanaar and R Gelinas and JC Dorsman",

year = "2015",

doi = "10.1038/ncomms9829",

language = "Undefined/Unknown",

volume = "6",

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, Altelaar, AFM, Meijers-Heijboer, H, Joenje, H, Glusman, G, Roach, J, Hood, L, Galas, D, Wyman, CL, 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. https://doi.org/10.1038/ncomms9829

TY - JOUR

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

AU - Ameziane, N

AU - May, P

AU - Haitjema, A

AU - van de Vrugt, HJ

AU - van Rossum-Fikkert, SE

AU - Ristic, D.

AU - Williams, GJ

AU - Balk, J

AU - Rockx, D

AU - Li, H

AU - Rooimans, MA

AU - Oostra, AB

AU - Velleuer, E

AU - Dietrich, R

AU - Bleijerveld, OB (Onno)

AU - Altelaar, AFM

AU - Meijers-Heijboer, H

AU - Joenje, H

AU - Glusman, G

AU - Roach, J

AU - Hood, L

AU - Galas, D

AU - Wyman, C.L.

AU - Balling, R

AU - den Dunnen, J

AU - de Winter, JP (Johan)

AU - Kanaar, Roland

AU - Gelinas, R

AU - Dorsman, JC

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 - 10.1038/ncomms9829

DO - 10.1038/ncomms9829

M3 - Article

SN - 2041-1723

VL - 6

JO - Nature Communications

JF - Nature Communications

ER -