Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer


PALB2 was recently identified as a nuclear binding partner of BRCA2. Biallelic BRCA2 mutations cause Fanconi anemia subtype FA-D1 and predispose to childhood malignancies. We identified pathogenic mutations in PALB2 (also known as FANCN) in seven families affected with Fanconi anemia and cancer in early childhood, demonstrating that biallelic PALB2 mutations cause a new subtype of Fanconi anemia, FA-N, and, similar to biallelic BRCA2 mutations, confer a high risk of childhood cancer.

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Figure 1: Evidence that PALB2 deficiency causes FA-N.


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We would like to thank all the families with Fanconi anemia for cooperating in this study and the many physicians that have referred families for participation in the research. In particular, we thank the doctors and counselors who provided samples and information from the FA-N cases, including R. Beier, T. Brenn, R.C. Lewandowski, M. Hamre, R.E. Harris, A. Carlson, V.M. Der Kaloustian, N. Wong and M. Buyukpamukcu. We thank B. Xia and D. Livingston for the PALB2 antibody and the pOZC-PALB2 vector; K. Spanova and S. Fielding for technical assistance with PALB2 sequencing; R. Friedl, B. Gottwald and S. Furlan for the flow cytometry analyses and handling of patients' cells and M. Stratton, A. Futreal and R. Scott for comments on the manuscript. We acknowledge use of controls from the British 1958 Birth Cohort DNA collection, funded by the Medical Research Council grant G0000934 and the Wellcome Trust grant 068545/Z/02. This work forms part of the UK Childrens' Cancer and Leukaemia Group's FACT (Factors Associated with Childhood Tumours) Study. The work was supported in part by the following: R37HL32987 and R01CA82678 from the US National Institutes of Health (A.D.A.); the Daniel Ayling Fanconi Anaemia Trust (C.G.M.); the Deutsche Fanconi-Anamie-Hilfe e V., Schroeder-Kurth-Fond and the Fanconi Anemia Research Fund (D.S., H.H.); the Deutsche Forschungsgemeinschaft and Elterninitiative Kinderkrebsklinik Duesseldorf e. V. (H.H.); the Jewish General Hospital Weekend to End Breast Cancer, Rethink Breast Cancer, Canada and Canadian Foundation for Innovation (M.T.); the Breast Cancer Campaign (P.K.) and, primarily, the Institute of Cancer Research and Cancer Research UK (S.R., S.H., K.B., S.S., N.R.).

Author information




The study was designed by N.R. The mutational and PALB2 protein blot analyses were performed by S.S., K.B., S.H., P.K. and S.S. under the direction of N.R. The cellular, protein blot and complementation analyses and investigation of effects of splicing mutations were performed by D.S., H.H., R.K., K.N., M.F., M.W. and H.N. The phenotypic assessment, sample collection and characterization with respect to Fanconi anemia subgroups was performed by D.S., H.H., S.D.B., F.P.L., S.Y., H.A., M.T., C.G.M. and A.D.A. The manuscript was written by N.R with contributions from the other authors.

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Correspondence to Nazneen Rahman.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Cellular phenotype of PALB2 deficiency. (PDF 1458 kb)

Supplementary Table 1

Primers and PCR conditions for PALB2 coding exons. (PDF 27 kb)

Supplementary Methods (PDF 94 kb)

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Reid, S., Schindler, D., Hanenberg, H. et al. Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nat Genet 39, 162–164 (2007).

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