RESUMO
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.
RESUMO
BACKGROUND: The coronavirus pandemic has exerted significant impacts on primary care, causing rapid digital transformation, exacerbating social isolation, and disrupting medical student and General Practice [GP] trainee education. Here we report on a medical student telephone initiative set-up by a final year GP trainee (the equivalent of a family medicine resident), which aimed to support patients at high risk and vulnerable to the Coronavirus Disease of 2019 [Covid-19]. In addition, it was hoped the project would mitigate a digital divide, enable proactive anticipatory planning, and provide an active learning environment to compensate for the pandemic's impact on medical education. METHODS: Thirty-three medical students conducted daily telephone conversations with high risk and vulnerable patients as specified by the initial NHSE published lists. They confirmed public health messages, offered details for voluntary support groups, established need for medication delivery, explored levels of digital connectivity, and prompted discussions around end-of-life choices. Students had access to online reflective resources and daily remote debriefing sessions with the GP trainee. A convergent mixed-methods evaluation was subsequently undertaken, using quantitative process and descriptive data and individual qualitative interviews were conducted according to a maximal variation sampling strategy with students, General Practitioners [GPs], and the GP trainee. Inductive thematic analysis was then applied with cross-validation, respondent validation, and rich evidential illustration aiding integrity. RESULTS: Ninety-seven 'high risk' and 781 'vulnerable' calls were made. Individuals were generally aware of public heath information, but some struggled to interpret and apply it within their own lives. Therefore respondents felt students provided additional practical and psychological benefits, particularly with regard to strengthening the links with the community voluntary groups. The project was widely liked by students who reported high levels of skill development and widened awareness, particularly valuing the active learning environment and reflective feedback sessions. CONCLUSION: This study demonstrates utilization of medical students as wider assets within the primary health care team, with an initiative that enables support for vulnerable patients whilst promoting active medical education. Ongoing integration of students within 'normal' primary health care roles, such as chronic disease or mental health reviews, could provide similar opportunities for supported active and reflective learning.
