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Numeric sex chromosome abnormalities are commonly associated with an increased cancer risk. Here, we report a 14-year-old boy with a rare mosaic 45, X/48, XYYY karyotype presenting with subtle dysmorphic features and relative height deficiency, requiring growth hormone therapy. As only 12 postnatal cases have been described so far with very limited follow-up data, to assess the proband’s long-term prognosis, including cancer risk, we performed high-throughput single-cell RNA sequencing (scRNA-seq) analysis. Although comprehensive cytogenetic analysis showed seemingly near perfect balance between 45, X and 48, XYYY cell populations, scRNA-seq revealed widespread differences in genotype distribution among immune cell fractions, specifically in monocytes, B- and T-cells. These results were confirmed at DNA level by digital-droplet PCR on flow-sorted immune cell types. Furthermore, deregulation of predominantly autosomal genes was observed, including TCL1A overexpression in 45, X B-lymphocytes and other known genes associated with hematological malignancies. Together with the standard hematological results, showing increased fractions of monocytes and CD4+/CD8+T lymphocytes ratio, long-term personalized hemato-oncological surveillance was recommended in the reported patient.

Introduction: Individuals with monoallelic pathogenic variants in BRCA1/BRCA2 genes are at an in-creased risk of developing breast or ovarian cancer. Predictive testing is currently available, however, the results of genetic tests may present a stressor not only related to the fear associated with the impact of the diagnosis on an individual’s future but also the possibility of passing it on to offspring as well as re-ceiving it from ancestors. Aim: The aim of the study was to verify the level of depression, stress, and anxiety in individuals waiting for the results of BRCA genetic test in the context of personal and family history. How personality traits and stress coping strategies influence the level of stress, anxiety, and depression as well as social support was examined. Material and methods: 82 consecutive individuals eligible for BRCA testing according to criteria as in the Polish National Health Programme were invited to the study. Respondents completed an anonymous online survey consisting of basic information and five questionnaires: the Inventory for Measuring Coping with Stress (Mini-COPE), the Depression, Anxiety and Stress Scale (DASS-21), the Generalized Anxiety Disorder 7-Item Scale (GAD-7), Polish adaptation of the Ten Item Personality Inventory test (TIPI-PL), and the Berlin Social Support Scales (BSSS). Obtained scores were compared with respect to gender, prior fam-ily history of cancer, and status of the genetic test (pending vs. already delivered).Results and discussion: According to the Mini-COPE, participants obtained the highest scores in strate-gies: Active coping, Planning, Positive reframing, Acceptance, and Seeking emotional support. The results on every scale of the DASS-21 questionnaire were in the normal range. The GAD-7 results show that re-spondents were mainly at the level of minimal and mild anxiety. The highest scores in the TIPI-PL test were obtained by the respondents on the Conscientiousness, Agreeableness, and Extraversion scales, while men received higher results on the Emotional Stability scale, compared to women. In the BSSS, individu-als obtained the highest score on the Satisfaction of Received Support, and Perceived Available Instrumen-tal Support scales. Participants, who have already obtained the results of genetic test had higher score on the Need for Support scale. Conclusions: In the background of BRCA screening women are less emotionally stable and can experi-ence easier negative emotions, compared to men. In general, the situation of BRCA genetic testing is not causing significant negative mental discomfort. Nonetheless, the results indicate a significant role of so-cial support in coping with stress in individuals who have already obtained the results of their genetic test.

IntroductionIndividuals with monoallelic pathogenic variants in <i>BRCA1</i>/<i>BRCA2</i> genes are at an increased risk of developing breast or ovarian cancer. The results of genetic tests may present a stressor related to the fear associated with the impact of the diagnosis on an individual’s future.AimThe aim of the study was to verify the level of depression, anxiety, and stress in individuals waiting for the results of <i>BRCA</i> genetic tests. How personality traits, stress coping strategies and social support influence the level of mental discomfort was examined.Material and methods82 consecutive individuals completed an anonymous online survey consisting of basic information and five questionnaires: the Inventory for Measuring Coping with Stress (Mini-COPE), the Depression, Anxiety and Stress Scale (DASS-21), the Generalized Anxiety Disorder 7-Item Scale (GAD-7), Polish adaptation of the Ten Item Personality Inventory test (TIPI-PL), and the Berlin Social Support Scales (BSSS).Results and discussionParticipants obtained the highest scores in Mini-COPE strategies: active coping, planning, positive reframing, acceptance, and seeking emotional support. The results of DASS-21 and GAD-7 indicate the level of depression, anxiety, and stress mainly in the normal range. The highest scores in the TIPI-PL test were obtained on the conscientiousness, agreeableness, and extraversion scales. Participants, who have already obtained the results had higher scores on the Need for Support Scale (BSSS).ConclusionsIn general, the situation of <i>BRCA</i> genetic testing is not causing significant negative mental discomfort. Nonetheless, the results indicate a significant role of social support in coping with stress in individuals who have already obtained the results of their genetic test.