Germline sequence variation in cancer genes in Rwandan breast and prostate cancer cases.

Cancer genetic data from Sub-Saharan African (SSA) are limited. Patients with female breast (fBC), male breast (mBC), and prostate cancer (PC) in Rwanda underwent germline genetic testing and counseling. Demographic and disease-specific information was collected.

Germline and Somatic Fumarate Hydratase Testing in Atypical Uterine Leiomyomata.

Unlabelled: Women with germline pathogenic variants (PV) in the fumarate hydratase (FH) gene develop cutaneous and uterine leiomyomata and have an increased risk of developing aggressive renal cell carcinomas. Many of these women are unaware of their cancer predisposition until an atypical uterine leiomyoma is diagnosed during a myomectomy or hysterectomy, making a streamlined genetic counseling process after a pathology-based atypical uterine leiomyoma diagnosis critical. However, the prevalence of germline pathogenic/likely PVs in FH among atypical uterine leiomyomata cases is unknown.

Advancing Precision Oncology in Hereditary Paraganglioma-Pheochromocytoma Syndromes: Integrated Interpretation and Data Sharing of the Germline and Tumor Genomes.

Standard methods of variant assessment in hereditary cancer susceptibility genes are limited by the lack of availability of key supporting evidence. In cancer, information derived from tumors can serve as a useful source in delineating the tumor behavior and the role of germline variants in tumor progression. We have previously demonstrated the value of integrating tumor and germline findings to comprehensively assess germline variants in hereditary cancer syndromes.

Development and evaluation of INTGRATE: a platform for comprehensive assessment of the role of germline variants informed by tumor signature profile in Lynch syndrome.

The presence of variants of uncertain significance (VUS) in DNA mismatch repair (MMR) genes leads to uncertainty in the clinical management of patients being evaluated for Lynch syndrome (LS). Currently, there is no platform to systematically use tumor-derived evidence alongside germline data for the assessment of VUS in relation to LS. We developed INTGRATE (INTegrated INTerpretation of GeRmline And Tumor gEnomes) to leverage information from the tumor genome to inform the potential role of constitutional VUS in MMR genes.

The CPT1A Arctic variant: perspectives of community members and providers in two Alaska tribal health settings.

Newborn screening in Alaska includes screening for carnitine palmitoyltransferase 1A (CPT1A) deficiency. The CPT1A Arctic variant is a variant highly prevalent among Indigenous peoples in the Arctic. In this study, we sought to elicit Alaska Native (AN) community member and AN-serving healthcare providers' knowledge and perspectives on the CPT1A Arctic variant.

Pretest Video Education Versus Genetic Counseling for Patients With Prostate Cancer: ProGen, A Multisite Randomized Controlled Trial.

Purpose: Germline genetic testing (GT) is recommended for men with prostate cancer (PC), but testing through traditional models is limited. The ProGen study examined a novel model aimed at providing access to GT while promoting education and informed consent.

Methods: Men with potentially lethal PC (metastatic, localized with a Gleason score of ≥8, persistent prostate-specific antigen after local therapy), diagnosis age ≤55 years, previous malignancy, and family history suggestive of a pathogenic variant (PV) and/or at oncologist's discretion were randomly assigned 3:1 to video education (VE) or in-person genetic counseling (GC).

Cancer surveillance for transgender and gender diverse patients with Lynch syndrome: a practice resource of the Collaborative Group of the Americas on Inherited Gastrointestinal Cancer.

Transgender and gender diverse (TGD) populations with hereditary cancer syndromes face unique obstacles to identifying and obtaining appropriate cancer surveillance and risk-reducing procedures. There is a lack of care provider knowledge about TGD health management. Lynch syndrome (LS) is one of the most common hereditary cancer syndromes, affecting an estimated 1 in 279 individuals.

Clinical Impact of Pathogenic Variants in DNA Damage Repair Genes beyond and in Breast and Ovarian Cancer Patients.

Consensus guidelines for hereditary breast and ovarian cancer include management recommendations for pathogenic/likely pathogenic (P/LP) variants in , , and other DNA damage repair (DDR) genes beyond or . We report on clinical management decisions across three academic medical centers resulting from P/LP findings in DDR genes in breast/ovarian cancer patients. Among 2184 patients, 156 (7.

Improving gender-affirming care in genetic counseling: Using educational tools that amplify transgender and/or gender non-binary community voices.

Transgender and/or gender non-binary (TGNB) individuals face significant health care disparities, including deficiencies in provider knowledge. To address this knowledge gap for genetic counselors, we developed, implemented, and analyzed an educational intervention on gender-affirming genetic counseling (GC) and care for TGNB patients. In partnership with the TGNB community, we designed a 5-module (length = 146 min ± 94 min) genetic counseling-targeted online learning program focused on gender-affirming care (Amplify).

Vulvar Melanoma in association with germline MITF p.E318K variant.

Vulvar melanoma is a rare and aggressive cancer with a poor prognosis. The etiology of mucosal melanoma remains largely uncharacterized and no hereditary risk factors are established for this rare disease. While the germline variant MITF p.

Transgender patients' perspectives on their cancer genetic counseling experiences.

Transgender (trans) individuals face many forms of discrimination in accessing health care, including lack of provider knowledge and denial of services. Barriers specific to the cancer setting include limited availability of information concerning cancer management and its potential impact on gender affirmation therapies and minimal training for providers regarding inclusive practices for the trans population. The limited research about the experiences of cancer genetic counseling for trans patients has investigated exclusively the perspective of the provider, not the patient.

Transgender and gender-diverse (TGD) individuals' perspectives on research seeking genetic variants associated with TGD identities: a qualitative study.

Recent genetic research has explored how genetic variants may contribute to gender dysphoria and transgender and gender-diverse (TGD) identities. When investigating communities that have been marginalized, it is important for researchers to incorporate perspectives of the communities the research is targeting. Therefore, investigators should incorporate the TGD community's opinions into this research to mitigate potential ethical issues, given the history of pathologization of TGD identities and utilization of genetics for eugenics.

Pathogenicity of VHL variants in families with non-syndromic von Hippel-Lindau phenotypes: An integrated evaluation of germline and somatic genomic results.

Von Hippel-Lindau (VHL) syndrome is a hereditary tumor syndrome associated with germline loss-of-function pathogenic variants (PVs) in the VHL gene. VHL is classically associated with a high penetrance for many different tumor types. The same tumors may be sporadic in the setting of somatic VHL PVs.

A resource of lipidomics and metabolomics data from individuals with undiagnosed diseases.

Every year individuals experience symptoms that remain undiagnosed by healthcare providers. In the United States, these rare diseases are defined as a condition that affects fewer than 200,000 individuals. However, there are an estimated 7000 rare diseases, and there are an estimated 25-30 million Americans in total (7.

Novel Pathogenic Germline Variant of the Adenomatous Polyposis Coli (APC) Gene, p.S2627Gfs*12 Identified in a Mild Phenotype of APC-Associated Polyposis: A Case Report.

BACKGROUND The diagnoses of adenomatous polyposis coli (APC)-associated polyposis conditions are typically based on suggestive personal features and/or family history, and the identification of a pathogenic variant in the APC gene. However, with large-scale genome sequencing, it is now possible to identify pathogenic variants before or even without the presentation of the expected clinical features. This case describes a novel pathogenic APC variant.

Correction: yippee like 3 (ypel3) is a novel gene required for myelinating and perineurial glia development.

[This corrects the article DOI: 10.1371/journal.pgen.

Genetic counseling following direct-to consumer genetic testing: Consumer perspectives.

As the use and scope of direct-to-consumer genetic testing (DTC GT), also becoming known as consumer-driven genetic testing, increases, consumers may seek genetic counseling to understand their results and determine healthcare implications. In this study, we interviewed individuals who sought genetic counseling after receiving DTC GT results to explore their motivations, expectations, and experiences. Participants were recruited from the Impact of Personal Genomics (PGen) Study, a longitudinal cohort study of DTC GT customers.

yippee like 3 (ypel3) is a novel gene required for myelinating and perineurial glia development.

Hypomyelination, a neurological condition characterized by decreased production of myelin sheets by glial cells, often has no known etiology. Elucidating the genetic causes of hypomyelination provides a better understanding of myelination, as well as means to diagnose, council, and treat patients. Here, we present evidence that YIPPEE LIKE 3 (YPEL3), a gene whose developmental role was previously unknown, is required for central and peripheral glial cell development.

Statistically Driven Metabolite and Lipid Profiling of Patients from the Undiagnosed Diseases Network.

Advancements in molecular separations coupled with mass spectrometry have enabled metabolome analyses for clinical cohorts. A population of interest for metabolome profiling is patients with rare disease for which abnormal metabolic signatures may yield clues into the genetic basis, as well as mechanistic drivers of the disease and possible treatment options. We undertook the metabolome profiling of a large cohort of patients with mysterious conditions characterized through the Undiagnosed Diseases Network (UDN).