Hereditary Risk Research Articles

Familial patterns of alopecia areata: A systematic review and meta-analysis.

Alopecia Areata (AA) is a T cell-mediated autoimmune disease characterized by sudden hair loss. It is associated with a significant familial predisposition and comorbidities such as thyroid disease, diabetes, atopic dermatitis, and vitiligo. This study aims to systematically review and meta-analyze the prevalence of familial AA and its associated comorbidities to better understand the hereditary nature of the disease. A systematic review and meta-analysis were conducted following the PRISMA guidelines. Relevant studies were identified from databases including EMBASE, Cochrane Library, PubMed, and Web of Science up to October 15, 2023. Studies were included if they reported on AA patients with a confirmed diagnosis and a family history of AA or related comorbidities. Data extraction and quality assessment were performed by two independent reviewers, with discrepancies resolved by a third reviewer. Pooled prevalence estimates were calculated using a random effects model. The meta-analysis included 67 studies, encompassing 24,226 AA patients and their relatives. The prevalence of a family history of alopecia areata (AA) was found to be 17.6%, indicating that 17.6% of individuals with AA have a positive family history of the condition. (CI: 14.9%-20.6%, I2=96%). The prevalence among relatives was 0.90% (CI: 0.55%-1.47%, I2=98%), with the highest prevalence observed in first-degree relatives at 3.22% (CI: 2.31%-4.48%, I2=94%). Comorbid conditions were present in 9.61% (CI: 6.98%-13.1%, I2=95%) of family members across first-, second-, and third-degree relatives of individuals with alopecia areata have comorbid autoimmune or related conditions, including thyroid disease (4.7%), diabetes (10.1%), atopic dermatitis (18.9%), vitiligo (5.5%), and other autoimmune disease (12.1%). This systematic review and meta-analysis highlight the significant familial risk and comorbidities in family members of AA patients. The findings emphasize the need for comprehensive family monitoring, which includes regular health screenings for autoimmune and related conditions among relatives of AA patients, and genetic counseling to educate families on hereditary risks and to guide early intervention and monitoring strategies. It can lead to improved outcomes. In the future, large population-based studies focusing on second and third-degree relatives are needed to further elucidate these associations.

Pediatric DTC Genetic Testing for Adult-Onset Inherited Cancer Risk: The Perspectives of High-Risk Parents.

Introduction Despite guidelines discouraging pediatric genetic testing for adult-onset hereditary cancer risk, direct-to-consumer (DTC) companies make them available to children's parents. This study examined the perspectives of high-risk parents towards such testing. Methods Interviews were conducted with N=30 parents (children ages 10-21) carrying pathogenic variants in cancer-causing genes available for detection through DTC tests. Interviews were analyzed inductively using a standardized methodology to identify prominent themes. Results Three major themes were identified: 1) high-risk parents' motivations for pediatric genetic testing, 2) risks and benefits of pediatric genetic testing, and 3) parental involvement of children in decision-making about testing. Although only n=5 parents (17% of the sample) reported that their children were genetically tested (n=3 through a DTC company, n=2 through a clinician), 73% endorsed pediatric genetic testing for general health reasons. Many parents (53%) expressed a preference for clinical testing over DTC testing. While parents recognized the limits of DTC testing, some (40%) expressed that it should remain available to high-risk parents for the purpose of identifying cancer risks in their children. Children's maturity (70%), interest in testing (77%), and anticipated responses to testing (43%) were cited as important decisional considerations. Conclusion Few high-risk parents utilized DTC testing for their children. Parents generally preferred the prospect of clinical testing, but some believed DTC testing should be an option available to families. Clinicians should discuss the risks and benefits of pediatric genetic testing, including DTC, with high-risk parents. This may facilitate more informed decision-making that minimizes potential harms.

Public perspectives on healthcare professional-directed communication of hereditary genetic risks: a mixed-method systematic review.

Genetic testing has revolutionized the identification of individuals at increased risk for various hereditary conditions, enabling early intervention and preventive measures. However, effective cascade counseling and testing depends on successful intra-familial communication. This mixed-method systematic review aimed to explore the general population's perspectives and preferences regarding the communication of potential genetic risk information by healthcare professionals. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered in the International Prospective Register of Systematic Reviews database (CRD42024532829). A comprehensive search of six databases yielded 17,292 records. After removing duplicates and screening for relevance, nine studies were included in the final analysis, conducted across diverse Western countries using both qualitative and quantitative designs. Results indicated a preference for healthcare-mediated communication, particularly through formal methods as letters, valued for their clarity and reliability. The role of family-mediated communication is nuanced, influenced by interpersonal relationship quality and the emotional burden of disclosing sensitive information. Ethical and legal considerations highlighted public support for overriding confidentiality in treatable conditions, while emphasizing respect for individual privacy and autonomy in untreatable conditions. This review underscores the importance of understanding public preferences to develop tailored communication strategies that balance professional involvement with respect for individual and familial dynamics. Healthcare professionals should be trained to provide empathetic, clear, and accurate information, considering the specific needs and contexts of at-risk individuals.

Response to Dapra comments on "How Hermann J. Muller Viewed the Ernest Sternglass Contributions to Hereditary and Cancer Risk Assessment".

Response to Dapra comments on "How Hermann J. Muller Viewed the Ernest Sternglass Contributions to Hereditary and Cancer Risk Assessment".

The Relationship of the Pathogenic Variant rs721048 in the Intron of the EHBP1 Gene with the Development of Prostate Cancer and Colorectal Cancer in the Kazakh Population

Background: Prostate cancer (PC) is one of the most common oncological diseases among men. Up to 20% of PC cases are associated with hereditary risks or syndromes. The impact of common variants, particularly EHBP1 c.1185+30064G>A rs721048, on developing PC and other malignancies remains unclear. There are also no data on the frequency of this variant in the Kazakh population or its association with PC, nor its potential connection with other malignancies, particularly colorectal cancer (CRC). Methods: We utilized the TruSight Cancer Sequencing Panel to assess pathological genomic variants in 72 male patients with histologically verified aggressive PC and 119 patients of Kazakh nationality with histologically confirmed CRC compared to the control group. Results: A variant in the intron of the EHBP1 gene c.1185+30064G>A rs721048 was identified in 18 patients (25%) out of 72 with PC, while in the control group of 41 healthy males, the rs721048 variant was found in only 4 (9.8%) individuals. In the CRC group, rs721048 was detected in 17 cases (14.2%) and eight control individuals (10%). Conclusions: The frequency of the EHBP1 c.1185+30064G>A rs721048 variant in the PC group was significantly higher (p < 0.05) than in healthy males of Kazakh nationality. Identifying EHBP1 c.1185+30064G>A among the male population of Kazakhstan will help form the high-risk groups for PC to prevent the development of malignant neoplasms. The presence of rs721048 was not significantly associated with the risk of developing CRC in our study.

Familial Polyposis and Colon Cancer

Familial adenomatous polyposis is an important hereditary risk factor for colon cancer. Such patients and families need special attention for prevention, early detection, and optimal treatment. Molecular testing is key to identify the specific mutation in the proband and can then make it easier to identify other family members at risk. Aggressive surveillance and colonoscopy will be indicated in most patients. Both colonic and extra-colonic manifestations are important. Chemoprevention is worth considering. Almost all patients will ultimately need colectomy. These details will be discussed in this review.

Personality traits of women with hereditary risk for breast/ovarian cancer versus obstetric history and cancer preventive behaviors

The aim of the study is to analyze the relationship between personality traits of women with hereditary predisposition to breast/ovarian cancer and their obstetric history and cancer-preventive behaviors. A total of 357 women, participants of ‘The National Program for Families With Genetic/Familial High Risk for Cancer’, were included in the study. The Neo Five-Factor Inventory (NEO-FFI) and a standardized original questionnaire designed for the purpose of the study were used. Breast ultrasound examination at a younger age was associated with Extraversion. Openness to Experience was linked with lower number of children, more frequent use of hormonal contraceptives, and younger age at first breast ultrasound examination. Women with higher Agreeableness scores were less likely to use contraceptives and underwent their first breast ultrasound later in life. Conscientiousness was associated with more frequent use of hormonal contraceptives and younger age at first breast ultrasound examination. Women at increased risk for developing breast/ovarian cancer who used hormonal contraceptives underwent breast ultrasound examinations earlier in life, while those who had breastfed their children chose to have their first mammogram earlier in life. Personality traits affect health-related behaviors and should be taken into account when designing theoretical models as well as interventions regarding health habits.

Professional improbity: How Hermann J. Muller's ethics affected his science.

The present paper provides an assessment of how the scientific and national policy achievements/goals of Hermann J. Muller were impacted by his ethics and provides several documented episodes in which Muller acted unethically to promote his personal gain-at the expense of others-within the scientific community. Muller manipulated the scientific community in self-serving ways to suppress perspectives that challenged his own views on radiation-induced gene mutation, and hereditary and cancer risk assessment in ways that influenced his significant awards (e.g., Nobel Prize in Medicine or Physiology), continued grant funding, and manifest effect on public health policy. Muller acted irresponsibly toward students and directed them to violate University of Texas policies that incurred severe student disciplinary actions (e.g., University suspension). Muller avoided responsibility by resigning from the University of Texas, avoiding a trial that could have led to his dismissal, and impacted his career achievements during the period of his nomination for the Nobel Prize. Muller was also a member of a US National Academy of Sciences Committee that committed scientific misconduct by misrepresenting the research record in ways that enhanced his continued funding support and fortified his influence on US health policy. The case of Muller is presented as a morality and object lesson worthy of consideration for current and future ethical conduct of scientific research.

Exploring the Role of Communication Asset Mapping (CAM) as a Strategy to Promote Hereditary Cancer Risk Assessment Information Within African American Communities.

Objective: African Americans (AAs) carry the largest burden for almost every type of cancer in the US and are also more likely to die from cancer. Approximately 10% of cancers can be explained by a hereditary factor and detected earlier. Many AAs, however, have inequitable access to hereditary cancer risk assessment (HCRA) tools and information, further exacerbating disparities in cancer rates. Innovative communication strategies to promote community-based HCRA information have promise as a means encouraging optimal primary cancer screening among AAs. The current pilot study followed a participatory process where researchers engaged with a Community Advisory Board (CAB) to explore how Communication Asset Mapping (CAM) could assist lay health advisors with the dissemination of evidence-based HC/RA information within AA faith communities. Methods: The research team and CAB conducted exploratory community-engaged group discussions with residents (n = 21) guided by Communication Infrastructure Theory, and used a community-engaged mapping process to inform the development of a CAM dissemination strategy. Results: Through textual analysis, the following conclusions were reached: (1) optimal locations (e.g., community centers) within specified neighborhood networks should have representatives who are trusted ambassadors to assist with HCRA information dissemination; (2) trusted community member voices should fully represent the neighborhood network in the community-engagement mapping process; (3) well-known and frequented geographic locations should provide a true representation of participants' neighborhoods to create a robust health information network concerning HCRA. Conclusions: Community residents appreciated the engagement process; however, they felt that its impact was limited due to the lack of community voices within their neighborhoods to identify important communication resources within the network for optimal HCRA information dissemination. CAM, therefore, is an important public health strategy for the identification of trusted networks and useful communication resources within these networks. The strategy was also helpful in pinpointing people who could be critical communicators of emerging health information akin to HCRA.

Prevalence and Causes of Neonatal Hearing Loss and Follow-Up Default in a Cohort from Saudi Arabia: A Retrospective Analysis

Background and Aims: The Universal Newborn Hearing Screening (UNHS) program in Saudi Arabia has proven instrumental in curbing the burden of neonatal hearing loss in the country. Recent studies from Saudi Arabia have shown a high rate of neonatal hearing loss and follow up default, along with poor awareness among parents, in the Madina region of the country. The study aimed to investigate the prevalence and causes of neonatal hearing loss and follow-up default, among newborns screened at the Children and Maternity Hospital in Madina, Saudi Arabia. Methods: All 500 neonates who were born at the hospital from January 2021 to January 2022, and underwent UNHS were included. Prevalence and causes were expressed as descriptive statistics. A chi-square test was used to correlate clinical risk factors with the occurrence of neonatal hearing loss. A P value <0.05 was considered statistically significant. Results: The prevalence of neonatal hearing loss was 1.2%, with 17.8% follow-up default. Exposure to ototoxic drugs, low birth weight, craniofacial anomalies, neonatal intensive care unit admission, maternal age >30 years, and hereditary risk showed a statistically significant correlation with neonatal hearing loss. Transportation difficulties (33.7%), lack of education (28.7%) and poor economic condition (21.8%) were the top causes of follow-up default. Conclusions: The study reiterates the dire need to raise awareness among parents of newborns regarding the detrimental effects of neonatal hearing loss, the importance of the UNHS program and the necessity for complete follow-up. A wider and more efficient network of screening and referral centers is needed. Research studies conducted at individual institutions can help identify and address the inadequacies of the UNHS program at a grassroots level.

MOLECULAR-BIOLOGICAL METHODS OF LABORATORY DIAGNOSTICS

The lecture highlights the fundamental concepts of molecular diagnostics. It presents insights into modern molecular-biological methods of laboratory diagnostics, emphasizing their role in detecting infectious agents, and gene mutations, and assessing hereditary disease risks. The material provides an in-depth overview of polymerase chain reaction (PCR) principles, DNA sequencing, hybridization techniques, and isoelectric focusing. Special attention is given to the advantages, challenges, and potential of these methods in clinical practice. Furthermore, the lecture discusses how molecular diagnostics supports personalized treatment approaches and emphasizes the importance of innovative equipment for effective pathology diagnostics.

Corporate Hereditary Succession Risk Management

The relevance of the study lies in the presence of problems related to hereditary transfer of business, especially in conditions of economic turbulence in the Russia, which, together with the loss of enterprises, can lead to the loss of accumulated knowledge and created technologies, which will put the Russian economy at a disadvantage compared to international competitors. In addition, this topic has not been sufficiently studied from the perspective of enterprise risk management. In the study, the factors of successful hereditary succession are divided into internal and external ones. External factors include a perfect regulatory framework and availability of necessary socio-economic infrastructure; internal factors include adherence to the principles of corporate governance G20/OECD, formation of a systematic approach to the transfer of the company to heirs, including development of their competencies, compliance with the legislative norms of the Russian Federation and formation of official succession plans. The purpose of the study is to develop a risk management mechanism for the hereditary succession of a corporation. Materials and methods. In the course of the research, the following methods were used: analysis of Russian and foreign scientific sources and business Internet resources, the case method, the «bow tie» risk management method (GOST R ISO/IEC 31010-2011), the scoring method based on the interpretation of scientific publications. Results. An event of hereditary succession, having a dual nature, like any risk, can affect the financial performance of the company, the image of the company in the eyes of the consumer (risks in brand management) and other aspects of the company's activities, that is why careful preparation and selection of the most favorable moment at the stage of the company's life cycle, for example, during its economic growth are necessary. The practical experience described in the article has shown that the absence of a regulated process for transferring business ownership leads to significant losses: closure of enterprises, financial damage to the company and heirs, complete loss of business, a decrease in market share, etc. An impulse mechanism for preventing the risk of hereditary succession has been identified in studying the experience of Chinese companies, which is implemented through one-time events, such as charitable donations to strengthen reputation. A systemic mechanism for preventing the risk of hereditary succession was identified from the experience of Auchan company, in which both the organizational structure and a set of measures were aimed at increasing the stability of the company in transferring business to heirs. It is proposed to introduce a hereditary succession risk management mechanism at the enterprise based on GOST R ISO/IEC 31010-2011. The use of the risk analysis method («bow tie») made it possible to systematize the causes, consequences and to offer a set of preventive (drawing up a legally formalized inheritance plan, training the heir in management skills, appointing intermediaries in conflict resolution, assessing market changes and adapting to them) and mitigating (creating a reserve fund in case of crisis situations, maintaining stable relationships with partners and clients, support for employees during the transition period, legal support) measures to prevent the risk of hereditary succession. The mechanism represents a cyclical sequence of stages aimed at continuous improvement of the risk management process during business transfer. The interdisciplinary approach at each stage is carried out with the help of a team of specialists, the contribution of each of whom is evaluated on a 10-point scale. Conclusions. The proposed mechanism can be adapted for various industries and types of family business and will help to mitigate the risks of hereditary succession, preserve the stability of enterprises and the Russian economy as a whole.

Germline pathogenic variants among high hereditary risk patients with breast and ovarian cancer and unaffected subjects in Lebanese Arab women

BACKGROUND The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries. AIM To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals. METHODS We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020. Data was collected and analyzed on Excel sheet. RESULTS In total, 358 individuals were included, including 257 patients and 101 unaffected individuals with relatives with breast or ovarian cancer. The prevalence of breast cancer susceptibility gene (BRCA) 1/2 pathogenic variants was 8.63% (19/220) in patients with breast cancer, and 15.1% (5/33) in those with ovarian cancer. Among the 25 of 220 patients with breast cancer tested by next-generation sequencing, 3 patients had pathogenic variants other than BRCA1/2 . The highest risk was observed in those aged 40 years with breast cancer and a positive family history, where the BRCA1/2 prevalence was 20.1% (9/43). Among the unaffected subjects, 31.1% (14/45) had the same BRCA1/2 pathogenic variants in their corresponding relatives. Among the subjects referred because of a positive family history of cancer without known hereditary factors, 5.35% (3/56) had pathogenic variants of BRCA1 and BRCA2 . The c.131G>T nucleotide change was noted in one patient and two unrelated unaffected subjects with a BRCA1 pathogenic variant. CONCLUSION This study showed a 8.63% prevalence of pathogenic variants in patients with breast cancer and a 15.1% prevalence in patients with ovarian cancer. Among the relatives of patients with BRCA1/2 pathogenic variants, 31% tested positive for the same variant, while 5.3% of subjects who tested positive due to a family history of breast cancer had a BRCA pathogenic variant.

The Role of Pharmacogenetic Testing in Optimizing Antipsychotic Therapy

Antipsychotic therapy in psychiatric practice can last from several months to many years, which requires the selection of drugs with the greatest effectiveness and the lowest risk of adverse drug reactions for the patient. According to experts, about a quarter of the total variability in response to antipsychotics is of genetic origin. This review analyzes and summarizes the results of domestic and foreign studies of the role of hereditary risk factors that cause a decrease in hepatic metabolism and efflux of antipsychotics due to polymorphism of genes encoding cytochrome P450 isoenzymes and transporter proteins. The key enzymes of antipsychotic metabolism registered for use in Russia and abroad are presented. The prospects of various options for pharmacogenetic testing in reducing the risk of potentially fatal complications in the selection of antipsychotic therapy in clinical practice are assessed.

A Global Perspective of GBA1-Related Parkinson's Disease: A Narrative Review.

Parkinson's disease (PD) is considered to be the second most prominent neurodegenerative disease and has a global prevalence. Glucocerebrosidase (GBA1) gene mutations represent a significant hereditary risk factor for the development of PD and have a profound impact on the motor and cognitive progression of the disease. The aim of this review is to summarize the literature data on the prevalence, type, and peculiarities of GBA1 mutations in populations of different ethnic backgrounds. We reviewed articles spanning the 2000-2024 period. GBA1-related PD has a worldwide distribution. It has long been recognized that pathogenic GBA1 mutations are particularly common in certain ethnic populations, including PD patients of Ashkenazi Jewish ancestry. Moreover, a considerable number of studies focused on European ancestry patients from Europe and North America have revealed a high proportion (up to 15%) of carriers among the PD population. GBA1 mutations also appear to play an important role in patient groups with an East Asian background, although the frequency of specific variants may differ as compared to those of European ancestry. Notably, the assessment of underrepresented populations in other parts of Asia (including India) and Latin America is in the spotlight of current research, while a variant with a newly described pathogenic mechanism has been reported in Sub-Saharan Africans. Given the importance of GBA1 mutations for PD genetics and clinical phenotype, a focused assessment of the prevalence and type of GBA1 variants in distinct ethnic populations will possibly inform ongoing PD-related clinical studies and facilitate upcoming therapeutic trials.

Online Screening and Virtual Patient Education for Hereditary Cancer Risk Assessment and Testing.

To use online screening and virtual patient education tools to improve the provision of hereditary cancer risk assessment. We conducted a prospective, single-arm study in which clinicians at five U.S. community obstetrics and gynecology practices underwent an 8-week observation followed by 3-4 weeks of training on online patient screening and virtual patient education (prerecorded video with or without a genetic counselor phone call) for genetic testing-eligible patients. After a 4-week practice period, hereditary cancer risk assessment and patient education metrics were collected at 8 weeks and compared with preintervention metrics using univariate conditional logistic regression models stratified by site. The primary outcome was the change in genetic testing completion rate. Clinicians and patients were invited to complete a satisfaction survey. A total of 5,795 and 5,135 patients were seen before and after the intervention, respectively. The proportion of screened patients meeting testing guidelines increased from 21.6% before the intervention to 28.2% after the intervention (odds ratio [OR] 1.36, 95% CI, 1.26-1.47, P<.001). Guideline-eligible patients were significantly more likely to be offered genetic testing (59.1% vs 89.1%, OR 2.06, 95% CI, 1.87-2.27, P<.001), to submit a sample (32.9% vs 45.0%, OR 1.49, 95% CI, 1.27-1.74, P<.001), and to complete testing (16.0% vs 34.2%, OR 2.38, 95% CI, 2.00-2.83, P<.001). Most clinicians agreed or strongly agreed that the screening tool improved the identification of patients meeting hereditary cancer risk assessment guidelines (92.1%), saved time (64.9%), and was easy to incorporate (68.4%) and that patient education improved their ability to deliver hereditary cancer risk assessment standard of care (84.2%). Most patients agreed or strongly agreed that virtual education helped them understand the purpose (91.7%) and implications (92.6%) of genetic testing. A guideline-based online patient screening tool and virtual patient education were well received. The online tool enabled identification of significantly more guideline-eligible candidates for hereditary cancer risk assessment, and education improved patients' genetic literacy. Together, these tools ultimately improved the genetic testing completion rate.

An eMERGEing definition of patient engagement in genetic counseling.

The concept of patient engagement has been widely studied for decades in the fields of medicine, nursing, psychology, social science, public health, and policy, and increased levels of patient engagement have been shown to improve health outcomes and strengthen reported experiences of care. Despite this, little research has been done to evaluate what patient engagement looks like within the context of a genetic counseling session. Additionally, there is limited literature from researchers based in the United States that aims to better understand patient engagement in non-English-speaking populations. This study is part of a larger protocol entitled "Multilingual Education Research in Genetic counseling Engagement (MERGE)," and it explores the elements that make up patient engagement in the context of pre-test genetic counseling for hereditary cancer risk among English- and Spanish-speaking patients. Eligible patients were 18 years or older at the time of their genetic counseling visit, had a personal or family history of breast cancer (if English-speaking) or a personal or family history of any cancer (if Spanish-speaking), and had not previously been seen for hereditary cancer genetic counseling. Out of 40 enrolled participants, 60% of patients (24/40) were English-speaking, while 40% of patients (16/40) were Spanish-speaking. In this study, English transcripts were generated from audio-recordings of clinical, standard-of-care genetic counseling sessions. The transcripts were qualitatively coded by two raters using an inductive approach, allowing for big Q thematic analysis. Six major themes were identified, describing ways in which patients show engagement and participate in decision-making during a pre-test genetic counseling session. All data were analyzed collectively, as assessment of differences between the language groups was not a primary analysis question. From the six themes, a definition of patient engagement in genetic counseling is proposed such that it consists of four "components" that together promote shared decision-making: Application of Education; Expression of Emotions; Feelings of Ownership; and Therapeutic Alliance. This working definition of patient engagement in genetic counseling has overlap with previous research on patient engagement in healthcare and with the Reciprocal-Engagement Model of genetic counseling. Future research on this topic can investigate methods for measuring and improving patient engagement across different settings and service delivery models.

A qualitative study of the experiences of patients with prostate cancer when receiving negative genetic results: "I still don't have a grasp of what it all means".

Germline genetic testing has been increasingly conducted for treatment implications in patients with prostate cancer due to the expansion of testing eligibility. Understanding patients' comprehension of genetic results is crucial for establishing effective result disclosure practices. This importance has grown due to the increasing prevalence of negative genetic results being conveyed via electronic communication and by providers without a genetics specialization. This study explores patients with prostate cancer's perceptions of genetic results communication. We analyzed 24 qualitative, semi-structured interviews with patients with prostate cancer at an urban safety-net hospital who had genetic results documented in their medical records. Interview questions focused on patient experiences with genetic referrals, genetic counseling, and genetic result disclosure. Audio recordings were professionally transcribed and analyzed by the study team utilizing an inductive thematic approach to generate themes from recurring codes. Of those who participated, 18 were interviewed in English, 5 in Spanish, and 1 in Haitian Creole. No participants reported having a pathogenic variant identified with genetic testing. Study participants identified a number of gaps in results communication which led to misconceptions regarding hereditary cancer risk. Three themes were generated: (1) Patients desired clear communication about the next steps after genetic testing, (2) Patients commonly experienced cognitive dissonance with negative genetic results given personal and family history of cancer, and (3) Patients felt reassurance from negative genetic results. This research suggests that maintaining conversations between patients and healthcare providers alongside the delivery of negative results assists in patient comprehension. Additionally, it is essential to evaluate the accessibility and appropriateness of notes and results sent to patients. Ultimately, understanding communication barriers in genetic results return is imperative in order to provide high-quality genetic care.

Prevalence and Determinants of Household Self-Reported Diabetes Mellitus in Gauteng, South Africa.

Diabetes mellitus is one of the leading causes of morbidity and mortality worldwide. Type 2 diabetes mellitus is the most prevalent type of diabetes mellitus, and it is associated with both hereditary and lifestyle risk factors. South Africa is not exempt from this pandemic; hence, this paper aims to assess the prevalence and determinants of household self-reported diabetes mellitus in Gauteng, South Africa. Data were sourced from the Gauteng City-Region Observatory (GCRO) quality of life survey (2020/2021). Bivariate and multivariate logistic regressions were applied. The prevalence of household self-reported diabetes mellitus in Gauteng was 11.1%. The 'other population' group (which included Whites, Coloureds and Indians), as well as older respondents, higher household monthly food expenditure, poor self-perceived health status and household self-reported hypertension were factors that increased the odds of household self-reported diabetes mellitus. Only informal housing decreased the odds of household self-reported diabetes mellitus. Screening of diabetes mellitus among those with poor living conditions, no medical aid and lack of access to healthcare facilities such as Gauteng township and informal settlement residents should be intensified. This secondary disease prevention intervention is crucial, as it will enhance the appropriate referrals and timeous chronic treatment for those with diabetes mellitus.

LNC-ing Genetics in Mitochondrial Disease.

Primary mitochondrial disease (MD) is a group of rare genetic diseases reported to have a prevalence of 1:5000 and is currently without a cure. This group of diseases includes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD), Leber's hereditary optic neuropathy (LHON), Leigh syndrome (LS), Kearns-Sayre syndrome (KSS), and myoclonic epilepsy and ragged-red fiber disease (MERRF). Additionally, secondary mitochondrial dysfunction has been implicated in the most common current causes of mortality and morbidity, including cardiovascular disease (CVD) and cancer. Identifying key genetic contributors to both MD and secondary mitochondrial dysfunction may guide clinicians to assess the most effective treatment course and prognosis, as well as informing family members of any hereditary risk of disease transmission. Identifying underlying genetic causes of primary and secondary MD involves either genome sequencing (GS) or small targeted panel analysis of known disease-causing nuclear- or mitochondrial genes coding for mitochondria-related proteins. Due to advances in GS, the importance of long non-coding RNA (lncRNA) as functional contributors to the pathophysiology of MD is being unveiled. A limited number of studies have thus far reported the importance of lncRNAs in relation to MD causation and progression, and we are entering a new area of attention for clinical geneticists in specific rare malignancies. This commentary provides an overview of what is known about the role of lncRNAs as genetic and molecular contributors to disease pathophysiology and highlights an unmet need for a deeper understanding of mitochondrial dysfunction in serious human disease burdens.