Childhood solid tumours cancer susceptibilityGene: FANCM
Publication PMID: 28837162 entitled: “Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility.” In this study breast cancer probands were investigated for DNA damage response genes, and 5 cases had FANCM loss-of-function variants. They showed a heterogeneous phenotype including cancer predisposition, toxicity to chemotherapy, early menopause, and possibly chromosome fragility. The phenotype severity might correlate with mutation position in the gene. They authors conclude: “Our 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.”
2 Nov 2017, 2:13 p.m.
Comment on list classification: This gene-disease relationship for Fanconi anaemia, biallelic variants, has only had one report, and has been refuted in a follow up study. PMID: 28376765 - reports a potentially pathogenic variant in FANCM variant in a cohort of paediatric patients with medulloblastoma; however it is unclear how many patients this was identified in, and the mode of inheritance for this variant.
26 Jul 2017, 11:59 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Comment on list classification: Changed rating of FANCM from Green to Red based on 2009 evidence that reclassifies earlier (2005) FA-M patient as FA-A.
28 Feb 2017, 2:04 p.m.
Further evidence that FANCM is not a Fanconi Anaemia gene comes from PMID:25078778: in a large exome-sequencing study and study of hospital records Lim et al., 2014 (PMID:25078778) did NOT find evidence to support FANCM as a gene associated with Fanconi Anaemia.
28 Feb 2017, 2:02 p.m.
FANCM was named as a Fanconi anemia gene based on Meetei et al., 2005 (PMID:16116422) who identified FANCM compound heterozygous variants in a cell line derived from a patient (EUFA867) with FA. They report that the patient's brother (also suffering from FA) carried the identical mutations in his blood DNA.
However, Singh et al., 2009 (PMID:19423727) found that patient EUFA867 also carries biallelic mutations in FANCA. Singh also noted that the FA-affected brother of EUFA867 carried the same biallelic FANCA variants, but only carried one of the FANCM variants, and thus they reclassified the sibling as being an FA-A patient.
28 Feb 2017, 2:02 p.m.
Rebecca Foulger: FANCM was named as a Fanconi a
Publications for FANCM were set to 19686080;28376765
This gene has been classified as Amber List (Moderate Evidence).
This gene has been classified as Red List (Low Evidence).
FANCM was added to Childhood solid tumourspanel. Source: Expert Review Green
FANCM was added to Childhood solid tumourspanel. Sources: Expert list
FANCM was created by ellenmcdonagh