Severe microcephalyGene: 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, 2:30 p.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).
9 Feb 2017, 11:35 a.m.
2nd March 2017: Panel review was assessed and panel was revised according to expert review and additional curation. This panel began with an expert gene list from Professor Andrew Jackson (University of Edinburgh) for primary microcephaly (MCPH) and microcephalic primordial dwarfism (MPD). Other disorders are included where microcephaly is a primary feature. Disorders where microcephaly is not the primary presenting feature are not included (e.g. congenital disorders of glycosylation, Proud syndrome, Norrie disease). The panel does not include disorders with a cortical malformation (e.g. lissencephaly) since the Malformations of cortical development' panel would be applied to these patients.
This gene has been classified as Red List (Low Evidence).
FANCM was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Other, Expert Review Green
FANCM was created by rfoulger