Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility

Research output: Contribution to journalArticle


PurposeMonoallelic germ-line mutations in the BRCA1/FANCS, BRCA2/FANCD1 and PALB2/FANCN genes confer high risk of breast cancer. Biallelic mutations in these genes cause Fanconi anemia (FA), characterized by malformations, bone marrow failure, chromosome fragility, and cancer predisposition (BRCA2/FANCD1 and PALB2/FANCN), or an FA-like disease presenting a phenotype similar to FA but without bone marrow failure (BRCA1/FANCS). FANCM monoallelic mutations have been reported as moderate risk factors for breast cancer, but there are no reports of any clinical phenotype observed in carriers of biallelic mutations.MethodsBreast cancer probands were subjected to mutation analysis by sequencing gene panels or testing DNA damage response genes.ResultsFive cases homozygous for FANCM loss-of-function mutations were identified. They show a heterogeneous phenotype including cancer predisposition, toxicity to chemotherapy, early menopause, and possibly chromosome fragility. Phenotype severity might correlate with mutation position in the gene.ConclusionOur data indicate that biallelic FANCM mutations do not cause classical FA, providing proof that FANCM is not a canonical FA gene. Moreover, our observations support previous findings suggesting that FANCM is a breast cancer-predisposing gene. Mutation testing of FANCM might be considered for individuals with the above-described clinical features.Genetics in Medicine advance online publication, 24 August 2017; doi:10.1038/gim.2017.123.


  • Irene Catucci
  • Ana Osorio
  • Brita Arver
  • Guido Neidhardt
  • Massimo Bogliolo
  • Federica Zanardi
  • Mirko Riboni
  • Simone Minardi
  • Roser Pujol
  • Jacopo Azzollini
  • Bernard Peissel
  • Siranoush Manoukian
  • Giovanna De Vecchi
  • Stefano Casola
  • Jan Hauke
  • Lisa Richters
  • Kerstin Rhiem
  • Rita K Schmutzler
  • Karin Wallander
  • Paolo Radice
  • Jordi Surrallés
  • Eric Hahnen
  • Javier Benitez
  • Paolo Peterlongo
External organisations
  • IFOM - The FIRC Institute of Molecular Oncology
  • Spanish National Cancer Research Center (CNIO)
  • Karolinska Institutet
  • University of Cologne
  • Istituto Nazionale dei Tumori
  • Cogentech
  • Karolinska University Hospital
  • Biomedical Network on Rare Diseases (CIBERER)
  • Autonomous University of Barcelona
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
Original languageEnglish
Pages (from-to)452–457
Number of pages6
JournalGenetics in Medicine
Early online date2017 Aug 24
Publication statusPublished - 2018
Publication categoryResearch