Genome-wide analysis of copy-number variation in humans with cleft lip and/or cleft palate identifies COBLL1, RIC1, and ARHGEF38 as clefting genes.

Cleft lip with or without cleft palate (CL/P) is a common birth defect with a complex, heterogeneous etiology. It is well established that common and rare sequence variants contribute to the formation of CL/P, but the contribution of copy-number variants (CNVs) to cleft formation remains relatively understudied. To fill this knowledge gap, we conducted a large-scale comparative analysis of genome-wide CNV profiles of 869 individuals from the Philippines and 233 individuals of European ancestry with CL/P with three primary goals: first, to evaluate whether differences in CNV number, amount of genomic content, or amount of coding genomic content existed within clefting subtypes; second, to assess whether CNVs in our cohort overlapped with known Mendelian clefting loci; and third, to identify unestablished Mendelian clefting genes. Significant differences in CNVs across cleft types or in individuals with non-syndromic versus syndromic clefts were not observed; however, several CNVs in our cohort overlapped with known syndromic and non-syndromic Mendelian clefting loci. Moreover, employing a filtering strategy relying on population genetics data that rare variants are on the whole more deleterious than common variants, we identify several CNV-associated gene losses likely driving non-syndromic clefting phenotypes. By prioritizing genes deleted at a rare frequency across multiple individuals with clefts yet enriched in our cohort of individuals with clefts compared to control subjects, we identify COBLL1, RIC1, and ARHGEF38 as clefting genes. CRISPR-Cas9 mutagenesis of these genes in Xenopus laevis and Danio rerio yielded craniofacial dysmorphologies, including clefts analogous to those seen in human clefting disorders.

Development and psychometric testing of the dyadic communication observational coding scheme in DEmentia care (DCODE): family dyadic communication in dementia.

OBJECTIVES: Understanding family dyadic communication in dementia is essential to promote the well-being of family caregivers and persons living with dementia. The Dyadic Communication Observational coding scheme in DEmentia care (DCODE) was developed and tested to assess family dyadic communication in dementia. METHODS: The DCODE was developed from a review of literature, expert review, and pretesting. A secondary analysis of the 75 in-home care video observations from 19 family caregiver-care recipient dyads was conducted to test psychometric properties. RESULTS: The DCODE consists of 43 caregiver items and 41 care recipient items. We observed internal consistency, intra-rater reliability, and inter-rater reliability as adequate. Content validity and convergent validity were moderate. Predictive validity was moderate in predicting caregiver burden. The overall psychometric properties demonstrated a moderate quality of the DCODE. CONCLUSIONS: Findings provided the preliminary psychometric evidence of the DCODE as a promising instrument to assess family dyadic communication in dementia. Future testing for concurrent, divergent, and structural validity of the DCODE is needed.

All things considered, my risk for diabetes is medium: A risk personalization process of familial risk for type 2 diabetes.

BACKGROUND: A positive family history of type 2 diabetes (T2D) has been associated with risk awareness and risk-reducing behaviours among the unaffected relatives. Yet, little is known about how people with a positive family history for diabetes develop and manage their personal sense of risk. OBJECTIVE: To characterize two key concepts, salience and vulnerability, within the familial risk perception (FRP) model among unaffected individuals, at increased familial risk for T2D. DESIGN: We conducted a mixed method study. Descriptions of salience and vulnerability were collected through semi-structured interviews. Participant's perception of self-reported risk factors (family history, age, race/ethnicity, medical history, weight and exercise) was measured using the Perceived Risk Factors for T2D Tool and was compared to a clinical evaluation of the same risk factors. RESULTS: We identified two components of salience: (a) concern for developing T2D and (b) risk awareness triggers, and two features of vulnerability: (a) statement of risk and (b) risk assessment devices. Although few participants (26%) were concordant between their perceived and clinical overall T2D risk, concordance for individual risk factors was higher, ranging from 42% (medical history) to 90% (family history). DISCUSSION AND CONCLUSION: Both familial and non-familial events lead people to contemplate their T2D risk, even among people who have a positive family history. Participants often downplayed their overall risk and underestimated their overall risk compared to a clinical risk assessment of the same self-reported risk factors. Clinicians could leverage key components of the FRP process as way to engage patients in risk reduction strategies earlier.

Bringing Personalized Medicine to a PACT Program: A Quality Improvement Project.

INTRODUCTION: Programs for assertive community treatment (PACT) serve persons with severe mental illness who have been unsuccessful with traditional outpatient services. Many PACT clients struggle to obtain symptom relief with medications that often have poor efficacy and undesired side effects, which can result in nonadherence, relapse, and increased health care utilization with associated costs. AIMS: This quality improvement project aimed to improve client and PACT program outcomes by incorporating pharmacogenomic testing into the psychopharmacological decision-making process. METHODS: The project used a pre-posttest design with each client serving as their own control to evaluate changes in clients' symptoms and program outcomes resulting from pharmacogenomics-guided medication management. RESULTS: Following project implementation, clients' symptoms were decreased and both engagement in care and stability in the community increased. Psychiatric hospitalizations and associated costs decreased. CONCLUSIONS: This project suggests utility for using pharmacogenomics testing to personalize care for persons with severe mental illness.

Establishing the Genomic Knowledge Matrix for Nursing Science.

PURPOSE: To establish the knowledge needed to integrate the multiple branches of omics into nursing research to accelerate achieving the research recommendations of the Genomic Nursing Science Blueprint. METHODS: The creation of the Genomic Knowledge Matrix occurred in three phases. In phase 1, the Omics Nursing Science and Education Network (ONSEN) Education Workgroup completed an evidence, bioinformatics, and technology review to inform the components of the Matrix. The ONSEN Advisory Panel then reviewed and integrated revisions. Phase 3 solicited targeted public comment focused on education and research experts, and applicable revisions were made. FINDINGS: The Genomic Knowledge Matrix establishes the following content areas: cellular and molecular biology, system physiology, microbiology, and translational bioinformatics as the minimum required preparation for nurse scientists to understand omics and to integrate this knowledge into research. The Matrix also establishes levels of understanding needed to function based on the role of the nurse scientist. CONCLUSIONS: The Genomic Knowledge Matrix addresses knowledge important for nurse scientists to integrate genomics into their research. Building on prior recommendations and existing genomic competencies, the Matrix was designed to present key knowledge elements critical to understand omics that underpin health and disease. Knowledge depth varies based on the research role. CLINICAL RELEVANCE: The Genomic Knowledge Matrix provides the vital guidance for training nurse scientists in the integration of genomics. The flexibility of the Matrix also provides guidance to inform fundamental genomic content needed in core science content in undergraduate and graduate level nursing curricula.

Type 2 diabetes familial risk personalization process profiles: Implications for patient-provider communication.

People who have a single first-degree relative with type 2 diabetes (T2D) are at increased risk for developing T2D over their lifetime. A positive family history of T2D is also associated with developing risk awareness and engaging in risk-reducing behaviors among the unaffected relatives. Yet, little is known about how people with a positive family history for disease personalize and process their familial risk to form perceptions about their own risk. In this mixed method study, we explored risk personalization among a diverse group of people between the ages of 18 and 60, with a positive family history of T2D, who were themselves unaffected (n = 109). We collected interview and survey data with respect to the familial risk perception personalization model. Using cluster analysis, qualitative and quantitative data were combined to inductively derive three distinct clusters representing three different familial risk perception personalization processes. These results can serve as a basis for tailored interventions aimed at reducing risk for T2D among people with increased risk due to familial history.

Family Communication About Genetic Risk of Hereditary Cardiomyopathies and Arrhythmias: an Integrative Review.

Screening for hereditary cardiomyopathies and arrhythmias (HCA) may enable early detection, treatment, targeted surveillance, and result in effective prevention of debilitating complications and sudden cardiac death. Screening at-risk family members for HCA is conducted through cascade screening. Only half of at-risk family members are screened for HCA. To participate in screening, at-risk family members must be aware of their risk. This often relies on communication from diagnosed individuals to their relatives. However, family communication is not well understood and is ripe for developing interventions to improve screening rates. Until very recently, family communication of genetic risk has been mostly studied in non-cardiac disease. Using this non-cardiac literature, we developed the family communication of genetic risk (FCGR) conceptual framework. The FCGR has four main elements of the communication process: influential factors, communication strategies, communication occurrence, and reaction to communication. Using the FCGR, we conducted an integrated review of the available literature on genetic risk communication in HCA families. Descriptive analysis of 12 articles resulted in the development of categories describing details of the FCGR elements in the context of HCA. This review synthesizes what is known about influential factors, communication strategies, communication occurrence, and outcomes of communication in the context of HCA.

Mental Models of Cause and Inheritance for Type 2 Diabetes Among Unaffected Individuals Who Have a Positive Family History.

Using the familial risk perception (FRP) model as a framework, we elicited causal and inheritance explanations for type 2 diabetes (T2D) from people who do not have T2D but have a family history for it. We identified four composite mental models for cause of T2D: (a) purely genetic; (b) purely behavioral/environmental; (c) direct multifactorial, in which risk factors interact and over time directly lead to T2D; and (d) indirect multifactorial, in which risk factors interact and over time cause a precursor health condition (such as obesity or metabolic syndrome) that leads to T2D. Interestingly, participants described specific risk factors such as genetics, food habits, lifestyle, weight, and culture as "running in the family." Our findings provide insight into lay beliefs about T2D that can be used by clinicians to anticipate or make sense of responses to questions they pose to patients about mental models for T2D.

Communication about Congenital Adrenal Hyperplasia: Perspective of Filipino Families.

Congenital adrenal hyperplasia (CAH), like other genetic conditions, is a relational disease from both the biological and psychosocial perspectives since the diagnosis gives rise to a variety of health, reproductive, and psychosocial implications. It is in these contexts that family communication of genetic information is important to study. Hence, this research aimed to explore genetic information communication in Filipino families affected with CAH. Using a qualitative descriptive design, families with a child affected with CAH were recruited through the CAH parent support group and were interviewed. Semi-structured interviews explored flow and content of genetic information communicated, the meanings the families attach to the communicated information, and the motivating and hindering factors in communication. Thematic analysis was used to analyze the findings. A total of five families participated, which included 11 individuals. Findings revealed that the diagnosis of CAH is not kept secret and it is openly shared with the family. The decision to communicate is influenced by several factors including the family's desire to seek further information about their family history. Initially, the focus of the communicated information is on the health implications and while communication about genetics occurs, this is almost always confined to the immediate family. The mother and grandmother serve as primary communicators in the family. The families have limited understanding of CAH especially its genetic implications including recurrence risk and carrier status. The findings can guide genetic counselors in supporting families in communicating information about CAH with the rest of the family.

Women's knowledge and use of prenatal screening tests.

AIMS AND OBJECTIVES: The aim of the study was to determine the rate of use of prenatal screening tests and the factors affecting the decision to have a prenatal screening test in pregnant women in Turkey. BACKGROUND: Prenatal genetic screening as an optional service is commonly used to determine a level of risk for genetic conditions in the foetus. DESIGN: A quantitative cross-sectional survey. METHODS: Pregnant women (n = 274) who sought prenatal care from one hospital in Turkey were recruited and asked to complete questionnaires that were developed by the researchers. Descriptive and inferential statistics were used to analyse the data. RESULTS: Almost half (44·2) % of the women were primiparas, and the majority (97·8%) were in the third trimester of pregnancy. Only 36·1% of the women reported that they had prenatal screening by either the double test or triple test. Women had a low level of knowledge regarding prenatal screening: the mean knowledge score was 3·43 ± 3·21 of a possible score of 10. Having consanguineous marriage, a history of spontaneous abortion, a child with genetic disorder, multiparity or a longer marriage duration were positively correlated with accepting a prenatal screening test. CONCLUSIONS: This study has provided baseline data on the uptake and reasons for accepting or declining a prenatal screening in a cohort of Turkish women. There is evidence to suggest that more education is needed to improve knowledge and provide comprehensive nursing care to promote informed consent in this context. RELEVANCE TO CLINICAL PRACTICE: Perinatal nurses are ideally situated to inform pregnant women about prenatal screening tests to improve access to healthcare services and to ensure informed decisions are made by pregnant women and their partners.

Five-Year Bibliometric Review of Genomic Nursing Science Research.

PURPOSE: This bibliometric review profiles the focus, dissemination, and impact of genomic nursing science articles from 2010 to 2014. DESIGN: Data-based genomic nursing articles by nursing authors and articles by non-nurse principal investigators funded by the National Institute of Nursing Research were categorized into the Genomic Nursing Science Blueprint nursing areas. METHODS: Bibliometric content analysis was used. FINDINGS: A total of 197 articles met the inclusion criteria. Of these, 60.3% were on biologic plausibility, 12.1% on client self-management, 11.1% on decision making or decision support, 8.1% on family, and 4.0% on communication, with the remaining 4.0% of articles focused on other topics. Few (11.6%) addressed healthcare disparities in the study purpose. Thirty-four references (17.2%) were cited 10 or more times. CONCLUSIONS: Research-based genomic nursing science articles are in the discovery phase of inquiry. All topics were investigated in more than one country. Healthcare disparities were addressed in few studies. Research findings from interdisciplinary teams were disseminated beyond nursing audiences, with findings addressing biologic discovery, decision making or support, and family being cited most frequently. Gaps in the reviewed articles included cross-cutting themes, ethics, and clinical utility. Interdisciplinary research is needed to document clinical and system outcomes of genomic nursing science implementation in health care. CLINICAL RELEVANCE: Although the review identifies areas that are encountered in clinical practice, relevance to practice will depend on evaluation of findings and subsequent development of clinical guidelines.

Educating future nursing scientists: Recommendations for integrating omics content in PhD programs.

Preparing the next generation of nursing scientists to conduct high-impact, competitive, sustainable, innovative, and interdisciplinary programs of research requires that the curricula for PhD programs keep pace with emerging areas of knowledge and health care/biomedical science. A field of inquiry that holds great potential to influence our understanding of the underlying biology and mechanisms of health and disease is omics. For the purpose of this article, omics refers to genomics, transcriptomics, proteomics, epigenomics, exposomics, microbiomics, and metabolomics. Traditionally, most PhD programs in schools of nursing do not incorporate this content into their core curricula. As part of the Council for the Advancement of Nursing Science's Idea Festival for Nursing Science Education, a work group charged with addressing omics preparation for the next generation of nursing scientists was convened. The purpose of this article is to describe key findings and recommendations from the work group that unanimously and enthusiastically support the incorporation of omics content into the curricula of PhD programs in nursing. The work group also calls to action faculty in schools of nursing to develop strategies to enable students needing immersion in omics science and methods to execute their research goals.

Communication Patterns and Characteristics of Family Caregivers and Persons Living With Dementia: Secondary Analysis of Video Observation.

BACKGROUND: It is essential to characterize communication patterns for better health outcomes for family caregivers and persons living with dementia. OBJECTIVE: This study aimed to examine the relationships between communication patterns and the characteristics of dyads of family caregivers and persons living with dementia. METHODS: A secondary analysis was conducted using 75 video-recorded home care observations from 19 dyads. Participant characteristics and caregiver burden, depression, and sense of competence were collected from the parent study. The video-recorded dyadic communication patterns were assessed using a coding scheme developed based on Communication Accommodation Theory and Classical Test Theory. The relative frequency of the communication patterns was compared between groups. RESULTS: Overall, 8311 caregiver and 8024 care recipient communication behaviors were observed. Caregiver communication patterns were categorized as facilitative, disabling, and neutral. Care recipient communication patterns were categorized as engaging, challenging, and neutral. Caregiver gender, care recipient gender, care recipient education level, dementia diagnosis length, types of dementia, dyadic gender difference, burden, depression, and competence of caregiver, and types of communication were significantly associated with caregiver communication. Dementia diagnosis length, caregiver competence, dyadic gender difference, and types of communication were significantly associated with care recipient communication. CONCLUSIONS: The findings demonstrated different communication patterns depending on individual and dyad characteristics and evidence for dyadic communication support to promote meaningful interaction for persons living with dementia. Further analysis is needed to identify mediating factors and causal relationships.

Parental perspectives on the diagnostic process for Duchenne and Becker muscular dystrophy.

Duchenne and Becker muscular dystrophy (DBMD) are allelic, X-linked recessive, neuromuscular disorders characterized by progressive loss of muscle function. Despite technological advances in diagnostic genetic testing, the mean age at diagnosis (4.7 years) has remained unchanged for decades. The purpose of the study was to characterize parental perceptions of the diagnostic process and identify factors that influence the timeline. Data collection for this qualitative study consisted of six individual and five group interviews. Participants (N = 30) included Hispanic, non-Hispanic black, and non-Hispanic white parents whose son was diagnosed with DBMD. The "help-seeking behavior model" provided an analytical framework to analyze the data. Parents did not move through help-seeking stages unidirectionally as described in other studies. Delays existed at each stage. We identified personal, familial, social, cultural, and provider factors that impeded earlier diagnosis. These barriers prolonged movement through a stage or led families to repeat previous stages. Results should initiate debate among system administrators, patient advocates, and healthcare providers regarding which barriers may be most modifiable and which interventions may reduce the time to diagnosis and limit parental emotional distress.

A closer look at the recommended criteria for disclosing genetic results: perspectives of medical genetic specialists, genomic researchers, and institutional review board chairs.

Next generation sequencing offers benefit of improved health through knowledge, but comes with challenges, such as inevitable incidental findings (IFs). The applicability of recommended criteria for disclosure of individual results when applied to disclosure of IFs is not well known. The purpose of this study was to examine how medical genetic specialists, genomic researchers, and Institutional Review Board (IRB) chairs perceive the importance of recommended criteria when applied to genetic/genomic IFs. We conducted telephone interviews with medical genetic specialists (genetic counselors, genetic nurses, medical geneticists, laboratory professionals), genomic researchers, and IRB chairs (N = 103). Respondents rated and discussed the importance of nine recommended criteria regarding disclosure of genetic/genomic IFs. Stakeholders agreed the most important criteria for disclosure were: (1) the IF points to a life-threatening condition; (2) there is a treatment; (3) individuals indicate in writing they wanted to be informed of IFs. Criteria rated less important were: analytic validity, high penetrance, association with a young age of onset and relative risk more than 2.0. Respondents indicated that some technical criteria were confusing, and in need of context. Our findings suggest that development of guidelines regarding management of IF include multiple stakeholders' perspectives and be based on a common language.

Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes.

Interferon regulatory factor 6 (IRF6) belongs to a family of nine transcription factors that share a highly conserved helix-turn-helix DNA-binding domain and a less conserved protein-binding domain. Most IRFs regulate the expression of interferon-alpha and -beta after viral infection, but the function of IRF6 is unknown. The gene encoding IRF6 is located in the critical region for the Van der Woude syndrome (VWS; OMIM 119300) locus at chromosome 1q32-q41 (refs 2,3). The disorder is an autosomal dominant form of cleft lip and palate with lip pits, and is the most common syndromic form of cleft lip or palate. Popliteal pterygium syndrome (PPS; OMIM 119500) is a disorder with a similar orofacial phenotype that also includes skin and genital anomalies. Phenotypic overlap and linkage data suggest that these two disorders are allelic. We found a nonsense mutation in IRF6 in the affected twin of a pair of monozygotic twins who were discordant for VWS. Subsequently, we identified mutations in IRF6 in 45 additional unrelated families affected with VWS and distinct mutations in 13 families affected with PPS. Expression analyses showed high levels of Irf6 mRNA along the medial edge of the fusing palate, tooth buds, hair follicles, genitalia and skin. Our observations demonstrate that haploinsufficiency of IRF6 disrupts orofacial development and are consistent with dominant-negative mutations disturbing development of the skin and genitalia.

Mutations in BMP4 are associated with subepithelial, microform, and overt cleft lip.

Cleft lip with or without cleft palate (CL/P) is a complex trait with evidence that the clinical spectrum includes both microform and subepithelial lip defects. We identified missense and nonsense mutations in the BMP4 gene in 1 of 30 cases of microform clefts, 2 of 87 cases with subepithelial defects in the orbicularis oris muscle (OOM), 5 of 968 cases of overt CL/P, and 0 of 529 controls. These results provide confirmation that microforms and subepithelial OOM defects are part of the spectrum of CL/P and should be considered during clinical evaluation of families with clefts. Furthermore, we suggest a role for BMP4 in wound healing.

A practical first step to integrating genetics into the curriculum.

We conducted a systematic literature review to identify tools that could be used to measure faculty and undergraduate nursing students' genetic literacy, and we assessed the utility of one of those tools, the Genetic Literacy Assessment Instrument (GLAI), with faculty and students at a college of nursing in a large public university. No significant differences were noted between faculty and students in terms of their overall scores on the GLAI. On average, faculty answered 76% of the questions correctly and students answered 73% of the questions correctly. Both groups scored highest in the genetics and society domain (93% and 85% correct answers for faculty and students, respectively) and lowest in the evolution domain (52% correct for both groups). The GLAI may be used to evaluate curricula for strengths and deficiencies, as well as to identify students and faculty in need of additional instruction.

Innovative Management of Nursing Student COVID-19 Cases and High-Risk Exposures.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) pandemic created significant disruption in higher education, especially in health science colleges where in-person and hands-on patient-facing learning environments are essential. Student monitoring and follow-up was an essential aspect of in-person learning for the fall 2020 semester. METHOD: Senior leaders and faculty in a college of nursing developed and implemented an innovative college-based COVID-19 management system to ensure real-time response to prolonged pandemic-related student absences. RESULTS: Decisions made from this management system allowed leaders within the college to implement programmatic changes to ensure student and faculty well-being. Furthermore, the COVID-19 management system allowed for close student follow-up through phone calls with a faculty member to ensure student well-being. CONCLUSION: Monitoring helped ensure appropriate physical and mental health services were accessible to students undergoing quarantine or self-isolation while also fostering positive student satisfaction throughout their prolonged absences. [J Nurs Educ. 2022;61(4):217-220.].

From Probands to Relatives: Communication of Genetic Risk for Hereditary Breast-Ovarian Cancer and Its Influence on Subsequent Testing.

BACKGROUND: The genetic risk communication from proband to relatives varies from family to family, and patients often need support with the communication of genetic test results and making decisions to manage hereditary cancer risks. OBJECTIVE: The aim of this study was to characterize the communication of BRCA1 or BRCA2 (BRCA1/2) genetic risk from proband to first-degree relatives (FDRs) using a social network framework. METHODS: We characterized network and nonnetwork factors to explore their association with which FDRs were told about the genetic risk and whether or not relatives underwent genetic testing. Ninety-two female probands with hereditary breast and ovarian cancer who have confirmed BRCA1/2 mutations participated in the study. Communication of hereditary breast and ovarian cancer risk was assessed between 92 probands and their 417 FDRs. RESULTS: Of 92 probands, 94.5% (n = 87) communicated their genetic test result to at least one of their FDRs. Of FDRs older than 18 years, 19.9% (n = 72) have genetic testing. Emotional closeness, educational level of the proband, and relative's age were significantly associated with communicating test results with FDRs. CONCLUSION: Communication of genetic risk with the FDRs after having a BRCA1/2 gene-mutation-positive test result was high in this group of cancer patients. However, the rate of genetic testing among FDRs was low. IMPLICATIONS FOR PRACTICE: Probands' educational level and age of relatives for cascade genetic screening should be considered during counseling. Interventions to support women with BRCA1/2 mutations during the communication process and their family members' engagement in testing and risk-reducing strategies are needed.