Anaemias and red cell disorders

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 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.”

Created: 2 Nov 2017, 2:03 p.m.

Comment on list classification: Changed rating from Green to Red based on 2009 evidence (PMID:19423727) that FANCM may not be responsible for the FA phenotypes reported in the original 2005 paper (PMID:16116422).

Created: 28 Feb 2017, 1:51 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 anemia.

Created: 9 Feb 2017, 1:26 p.m.

FANCM was named as a Fanconi anemia gene based on Meetei et al., 2005 (PMID:16116422) who identified compound heterozygous variants in the FANCM gene in a cell line derived from a patient with Fanconi anemia.

However, in cell lines derived from the 2 sibs originally reported by Meetei et al., Singh et al., 2009 (PMID:19423727) identified biallelic mutations in the FANCA gene. They also noted that only 1 of the sibs had clinical features of the disorder and that the clinically affected sib carried only 1 of the FANCM variants. The clinically unaffected sib carried both biallelic FANCA mutations and biallelic FANCM variants. Singh et al. (2009) reclassified the affected sib as having FANCA.

Created: 9 Feb 2017, 1:26 p.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