Journal article : Review
The emergence of Fanconi anaemia type S: a phenotypic spectrum of biallelic BRCA1 mutations
- Abstract:
- BRCA1 is involved in the Fanconi anaemia (FA) pathway, which coordinates repair of DNA interstrand cross-links. FA is a rare genetic disorder characterised by bone marrow failure, cancer predisposition and congenital abnormalities, caused by biallelic mutations affecting proteins in the FA pathway. Germline monoallelic pathogenic BRCA1 mutations are known to be associated with hereditary breast/ovarian cancer, however biallelic mutations of BRCA1 were long predicted to be incompatible with embryonic viability, hence BRCA1 was not considered to be a canonical FA gene. Despite this, several patients with biallelic pathogenic BRCA1 mutations and FA-like phenotypes have been identified - defining a new FA type (FA-S) and designating BRCA1 as an FA gene. This report presents a scoping review of the cases of biallelic BRCA1 mutations identified to date, discusses the functional effects of the mutations identified, and proposes a phenotypic spectrum of BRCA1 mutations based upon available clinical and genetic data. We report that this FA-S cohort phenotype includes short stature, microcephaly, facial dysmorphisms, hypo/hyperpigmented lesions, intellectual disability, chromosomal sensitivity to crosslinking agents and predisposition to breast/ovarian cancer and/or childhood cancers, with some patients exhibiting sensitivity to chemotherapy. Unlike most other types of FA, FA-S patients lack bone marrow failure.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.1MB, Terms of use)
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- Publisher copy:
- 10.3389/fonc.2023.1278004
Authors
+ National Institute for Health and Care Excellence
More from this funder
- Funder identifier:
- https://ror.org/015ah0c92
- Grant:
- CL-2018-13-005
- Programme:
- Clinical Lecturership in Paediatric Oncology
- Publisher:
- Frontiers Media
- Journal:
- Frontiers in Oncology More from this journal
- Volume:
- 13
- Article number:
- 1278004
- Place of publication:
- Switzerland
- Publication date:
- 2023-12-11
- Acceptance date:
- 2023-10-23
- DOI:
- EISSN:
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2234-943X
- Pmid:
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38146508
- Language:
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English
- Keywords:
- Subtype:
-
Review
- Pubs id:
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1595362
- Local pid:
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pubs:1595362
- Deposit date:
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2025-06-26
- ARK identifier:
Terms of use
- Copyright holder:
- Hughes and Rose
- Copyright date:
- 2023
- Rights statement:
- © 2023 Hughes and Rose. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
- Licence:
- CC Attribution (CC BY)
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