Radial dysplasia

Gene: 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.”

Created: 2 Nov 2017, 2:31 p.m.

Publications

• 28837162

Red List (low evidence)

Comment when marking as ready: Evidence not reached at present for causation. Therefore red.

Created: 11 May 2017, 11:58 a.m.

Comment when marking as ready: Insufficient evidence at present for causation in isolation

Created: 28 Feb 2017, 1:41 p.m.

Comment on list classification: See reviews for discussion of relative evidence for and against causation. The consensus on discussion amongst curation team was that the evidence presented suggests perhaps digenic contribution (FANCA / FANCM) in a patient. Therefore evidence not considered sufficient for inclusion. Await further reports.

Created: 28 Feb 2017, 1:40 p.m.

No current OMIM associated phenotype. Please see comprehensive assessment of the current evidence by Rebecca Foulger. In addition email correspondence with Noemi Roy, who has discussed with Inderjeet Dokal, an expert in this condition and the genes that are thought to be involved. He is aware of one family with compound het mutations in FANCM and FANCA.

It is possible that this gene is related to Fanconi anaemia but based upon the current evidence in my opinion it cannot be included for useful filtering of variants on a diagnostic basis unless further evidence of causation is identified.

Created: 28 Feb 2017, 9:51 a.m.

Mode of inheritance
Unknown

Publications

• 16116422
• 19423727
• 25078778

Comment on phenotypes: Removed 'Fanconi anemia, complementation group M, 614087' phenotype since MIM:614087 is no longer valid.

Created: 9 Feb 2017, 11:38 a.m.

Comment on list classification: Changed rating from Green to Red based on more recent evidence which disputes that FANCM is a Fanconi anemia gene (Singh et al., 2009 (PMID:19423727) and Lim et al., 2014 (PMID:25078778).

Created: 9 Feb 2017, 11:37 a.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Fanconi anemia

Publications

• 16116422

Variants in this GENE are reported as part of current diagnostic practice