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| Haematological malignancies cancer susceptibility v2.30 | ERCC6L2 |
Angela Hamblin gene: ERCC6L2 was added gene: ERCC6L2 was added to Haematological malignancies cancer susceptibility. Sources: Literature Mode of inheritance for gene: ERCC6L2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERCC6L2 were set to PMID: 30936069; PMID: 31221794 Phenotypes for gene: ERCC6L2 were set to Bone marrow failure syndrome 2, 615715; MDS; AML Review for gene: ERCC6L2 was set to GREEN gene: ERCC6L2 was marked as current diagnostic Added comment: ERCC6L2 is a relatively recently discovered gene in which biallelic germline LOF variants are associated with bone marrow failure syndrome and this gene already has green status is cytopenia panels on PanelApp. Over the last 3 years, with more widespread testing, it has become apparent that in addition to being associated with bone marrow failure it is also associated with the development of MDS / AML with the acquisition of pathogenic variants in the TP53 gene (lack of ERCC6L2 results in defects in the transcription-coupled nucleotide excision repair pathway, leading to genome instability). Initially described in Finland, a presentation at the American Society of Haematology 2021 https://doi.org/10.1182/blood-2021-145039 illustrated that there are a number of cases in other European countries now reported. I am aware that cases have also been detected within the GMS; the cytopenia panel has demonstrated the germline mutations, whereas these were not highlighted on the WGS performed for the subsequent AML owing to the fact the gene is not currently included on the applied germline panel. Detection of this germline variant is critical to management of these patients as currently it would mean an allogeneic HSCT is required (and as with any germline variant there would be implications for related donor choice). Sources: Literature |
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| Haematological malignancies cancer susceptibility | TP53 | Clare Turnbull reviewed TP53 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||