Information and genetic counselling for psychiatric risks in children with rare genomic disorders

AbstractPurposeGenomic medicine has transformed the diagnosis of neurodevelopmental disorders. Evidence of increased psychiatric comorbidity associated with genomic copy number and single nucleotide variants (CNV and SNV) may not be fully considered when providing genetic counselling. We explored parents’ experiences of genetics services and how they obtained information concerning psychiatric manifestations.MethodsParents of children diagnosed with genomic variants completed an online survey exploring, (i) how they experienced the genetic diagnosis, and (ii) how they acquired information about psychiatric, developmental and physical manifestations.ResultsTwo-hundred and 86 respondents completed the survey. Thirty percent were unsatisfied with receiving genetic diagnoses. Satisfaction was predicted if communication was by geneticists (p = 0.004); provided face-to-face (p = 0.003); clearly explained (p < 0.001); and accompanied by support (p = 0.017). Parents obtained psychiatric information from non-professional sources more often than developmental (ϕ 0.26, p < 0.001) and physical manifestations (ϕ 0.21, p = 0.003), which mostly came from health professionals. Information from support organisations was more helpful than from geneticists (odds ratio [OR] 21.0, 95% CI 5.1 – 86.8, p < 0.001); paediatricians (OR 11.0, 1.4 – 85.2, p = 0.004); and internet sites (OR 15.5, 3.7 – 64.8, p < 0.001).ConclusionA paucity of professional information about psychiatric risks after genetic diagnosis may impede early diagnosis and intervention for children with high genotypic risks. Planned integration of genomic testing into mainstream services should include genetic counselling training to address the full spectrum of developmental, physical and psychiatric manifestations and timely provision of high-quality information.

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Information and genetic counselling for psychiatric risks in children with rare disorders

10.1101/542423 ◽

2019 ◽

Author(s):

Andrew Cuthbert ◽

Aimee Challenger ◽

Jeremy Hall ◽

Marianne BM van den Bree

Keyword(s):

Mental Health ◽

Intellectual Disability ◽

Support Groups ◽

Genetic Counselling ◽

Odds Ratio ◽

Developmental Disorders ◽

Best Practice ◽

Genetic Diagnosis ◽

General Medicine ◽

Genomic Disorders

AbstractBackground:The diagnosis of developmental disorders is being transformed by advances in whole genome technologies. However, continuing uncertainties about the individual risks and potential severity of psychiatric impacts attributed to causal genomic variants limits the availability of comprehensive family-oriented information. In addition, there is insufficient evidence about how the parents of children with developmental disorders comprehend the facts and implications of their diagnosis through genetic counselling, nor how they gather developmental and mental health information to guide their understanding.Methods:Parents of children (aged 0–17 years) referred to paediatric genetics services completed an anonymous online 46-item survey about: (i) the experience of attending services to receive their child’s genetic diagnosis, and (ii) the availability, quality and helpfulness of information about psychiatric and neurodevelopmental conditions associated with genomic disorders.Findings:Two-hundred and eighty-six families (199 UK and 87 USA) completed the survey. One-in-three UK and one-in-five US respondents were dissatisfied with how their child’s genetic diagnosis was communicated. Satisfaction was predicted by face-to-face communication (odds ratio 2·91 [95% CI 1·43–5·94]; p=0·003); results being presented by genetics specialists (2·97 [1·41–6·26]; p=0·004); receiving clear explanations (5·14 [2·58– 10·26]; p<0·001); receiving support (2·99 [1·21–7·36], p=0·017); and male gender of the tested child (2·56 [1·28–5·14]; p=0·008). Compared to health-related information on developmental delay or intellectual disability, parents were more likely to obtain information about psychiatric manifestations from non-professional lay sources than from clinical specialists (p<0·001). This was particularly evident for families in the UK compared to the USA (p<0·001). Parents considered information from rare disorder support groups to be more helpful than from genetics specialists (odds ratio 11·0 [95% CI 5·08–86·75]; p<0·001), or paediatricians (11·0 [1·42–85·20]; p=0·006), or internet sites (15·5 [3·71–64·77]; p<0·001), which in turn proved more helpful than information provided by geneticists (2·5 [1·44–4·31]; p=0·001).Interpretation:Psychiatric comorbidity is a common feature of rare genomic disorders, but the paucity of suitable information available from clinical specialists suggests families are not optimally informed about these challenges. Wider implementation of genomic testing in general medicine should include adequate training in genetic counselling to ensure best practice in communicating and explaining complex test results supported by comprehensive, family-oriented information.Funding:The Waterloo Foundation: Changing Minds Programme (506296); The Medical Research Council (MRC) Research Grant: Intellectual Disability and Mental Health: Assessing Genomic Impact on Neurodevelopment (MR/N022572/1).

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Development of coupling controlled polymerizations by adapter-ligation in mate-pair sequencing for detection of various genomic variants in one single assay

DNA Research ◽

10.1093/dnares/dsz011 ◽

2019 ◽

Vol 26 (4) ◽

pp. 313-325 ◽

Cited By ~ 3

Author(s):

Zirui Dong ◽

Xia Zhao ◽

Qiaoling Li ◽

Zhenjun Yang ◽

Yang Xi ◽

...

Keyword(s):

Genetic Diagnosis ◽

Ease Of Use ◽

Nick Translation ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Genomic Variants ◽

Adapter Ligation ◽

Mate Pair ◽

Pair Method ◽

Genomic Disorders

Abstract The diversity of disease presentations warrants one single assay for detection and delineation of various genomic disorders. Herein, we describe a gel-free and biotin-capture-free mate-pair method through coupling Controlled Polymerizations by Adapter-Ligation (CP-AL). We first demonstrated the feasibility and ease-of-use in monitoring DNA nick translation and primer extension by limiting the nucleotide input. By coupling these two controlled polymerizations by a reported non-conventional adapter-ligation reaction 3′ branch ligation, we evidenced that CP-AL significantly increased DNA circularization efficiency (by 4-fold) and was applicable for different sequencing methods but at a faction of current cost. Its advantages were further demonstrated by fully elimination of small-insert-contaminated (by 39.3-fold) with a ∼50% increment of physical coverage, and producing uniform genome/exome coverage and the lowest chimeric rate. It achieved single-nucleotide variants detection with sensitivity and specificity up to 97.3 and 99.7%, respectively, compared with data from small-insert libraries. In addition, this method can provide a comprehensive delineation of structural rearrangements, evidenced by a potential diagnosis in a patient with oligo-atheno-terato-spermia. Moreover, it enables accurate mutation identification by integration of genomic variants from different aberration types. Overall, it provides a potential single-integrated solution for detecting various genomic variants, facilitating a genetic diagnosis in human diseases.

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Development of Coupling Controlled Polymerizations by Adapter-ligation in Mate-pair Sequencing for Detection of Various Genomic Variants in One Single Assay

10.1101/400689 ◽

2018 ◽

Author(s):

Zirui Dong ◽

Xia Zhao ◽

Qiaoling Li ◽

Zhenjun Yang ◽

Yang Xi ◽

...

Keyword(s):

Genetic Diagnosis ◽

Ease Of Use ◽

Nick Translation ◽

Single Nucleotide Variants ◽

Single Nucleotide ◽

Genomic Variants ◽

Adapter Ligation ◽

Mate Pair ◽

Pair Method ◽

Genomic Disorders

AbstractThe diversity of disease presentations warrants one single assay for detection and delineation of various genomic disorders. Herein, we describe a gel-free and biotin-capture-free mate-pair method through coupling Controlled Polymerizations by Adapter-Ligation (CP-AL). We first demonstrated the feasibility and ease-of-use in monitoring DNA nick-translation and primer extension by limiting the nucleotide input. By coupling these two controlled polymerizations by a reported non-conventional adapter ligation reaction 3’ branch ligation, we evidenced that CP-AL significantly increased DNA-circularization efficiency (by 4-fold) and was applicable for different sequencing methods but at a faction of current cost. Its advantages were further demonstrated by fully elimination of small-insert-contaminated (by 39.3-fold) with a ~50% increment of physical coverage, and producing uniform genome/exome coverage and the lowest chimeric rate. It achieved single-nucleotide variants detection with sensitivity and specificity up to 97.3 and 99.7%, respectively, compared with data from small-insert libraries. In addition, this method can provide a comprehensive delineation of structural rearrangements, evidenced by a potential diagnosis in a patient with oligo-atheno-terato-spermia. Moreover, it enables accurate mutation identification by integration of genomic variants from different aberration types. Overall, it provides a potential single-integrated solution for detecting various genomic variants, facilitating a genetic diagnosis in human diseases.

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A Better Learning Community: Mixed-Methods Reveal Medical Student Preferences with Implications for Learning Community Design and Implementation

Journal of Medical Education and Curricular Development ◽

10.1177/23821205211014895 ◽

2021 ◽

Vol 8 ◽

pp. 238212052110148

Author(s):

Jasna Vuk ◽

Steven McKee ◽

Sara Tariq ◽

Priya Mendiratta

Keyword(s):

Mixed Methods ◽

Learning Community ◽

Online Survey ◽

Free Form ◽

University Of Arkansas ◽

Medical Sciences ◽

Face To Face ◽

Personal Support ◽

School Learning ◽

The University

Background: Medical school learning communities benefit students. The College of Medicine (COM) at the University of Arkansas for Medical Sciences (UAMS) provides medical students with academic, professional, and personal support through a learning community (LC) made of 7 academic houses. Objectives: To evaluate the effectiveness of the academic house model at UAMS utilizing a mixed-methods survey. The aims were to: (1) assess student experience and satisfaction with academic houses, (2) describe the realms of advising and guidance, and (3) identify areas for improvement. Method: An online survey was assigned to 723 COM students (all students enrolled, first through fourth years) at UAMS in March 2019. The survey was comprised of 25 items (10 multiple-choice, 8 on the Likert scale, and 7 open-ended questions). Data was depicted using frequency and percentages and/or thematic review of free-form responses. Results: The survey response rate was 31% (227 students). The majority of students responding (132, 58.1%) attended 2 or more face-to-face meetings with the faculty advisor within the preceding year. However, 27 (11.9%) students did not have any meetings. Approximately two-thirds of the respondents were satisfied or very satisfied with the guidance and direction provided by their advisors [very satisfied (n = 83; 36.6%); satisfied (n = 77; 33.9%)]. Themes that emerged from student generated areas for improvement include time constraints, advisor/advisee interest mismatch, and perceived inadequacy of advising content/connections. Conclusions: This study confirms the effectiveness of the LC model for advising and mentoring in the COM at UAMS. Uniquely, this study identifies not only learners’ satisfaction with their LC but also highlights areas for improvement which are widely generalizable and important to consider for institutions with or planning to start an LC.

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Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns

Journal of Personalized Medicine ◽

10.3390/jpm11060562 ◽

2021 ◽

Vol 11 (6) ◽

pp. 562

Author(s):

Olga María Diz ◽

Rocio Toro ◽

Sergi Cesar ◽

Olga Gomez ◽

Georgia Sarquella-Brugada ◽

...

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Congenital Heart Defects ◽

Congenital Malformations ◽

Congenital Heart ◽

Heart Diseases ◽

Heart Defects ◽

Genetic Diagnosis ◽

Single Nucleotide Variants ◽

Personalized Approach

Congenital heart disease is a group of pathologies characterized by structural malformations of the heart or great vessels. These alterations occur during the embryonic period and are the most frequently observed severe congenital malformations, the main cause of neonatal mortality due to malformation, and the second most frequent congenital malformations overall after malformations of the central nervous system. The severity of different types of congenital heart disease varies depending on the combination of associated anatomical defects. The causes of these malformations are usually considered multifactorial, but genetic variants play a key role. Currently, use of high-throughput genetic technologies allows identification of pathogenic aneuploidies, deletions/duplications of large segments, as well as rare single nucleotide variants. The high incidence of congenital heart disease as well as the associated complications makes it necessary to establish a diagnosis as early as possible to adopt the most appropriate measures in a personalized approach. In this review, we provide an exhaustive update of the genetic bases of the most frequent congenital heart diseases as well as other syndromes associated with congenital heart defects, and how genetic data can be translated to clinical practice in a personalized approach.

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Are telephone consultations here to stay in rheumatology?

Rheumatology Advances in Practice ◽

10.1093/rap/rkaa071 ◽

2020 ◽

Author(s):

Sabrina R Raizada ◽

Natasha Cleaton ◽

James Bateman ◽

Diarmuid M Mulherin ◽

Nick Barkham

Keyword(s):

Older Patients ◽

Online Survey ◽

Vulnerable Groups ◽

Age Group ◽

Telephone Consultation ◽

Survey Tool ◽

Face To Face ◽

Vulnerable Patients ◽

Number Of Patients

Abstract Objectives During the COVID-19 pandemic, face-to-face rheumatology follow-up appointments were mostly replaced with telephone or virtual consultations in order to protect vulnerable patients. We aimed to investigate the perspectives of rheumatology patients on the use of telephone consultations compared with the traditional face-to-face consultation. Methods We carried out a retrospective survey of all rheumatology follow-up patients at the Royal Wolverhampton Trust who had received a telephone consultation from a rheumatology consultant during a 4-week period via an online survey tool. Results Surveys were distributed to 1213 patients, of whom 336 (27.7%) responded, and 306 (91.1%) patients completed all components of the survey. Overall, an equal number of patients would prefer telephone clinics or face-to-face consultations for their next routine appointment. When divided by age group, the majority who preferred the telephone clinics were <50 years old [χ2 (d.f. = 3) = 10.075, P = 0.018]. Prevalence of a smartphone was higher among younger patients (<50 years old: 46 of 47, 97.9%) than among older patients (≥50 years old: 209 of 259, 80.7%) [χ2 (d.f. = 3) = 20.919, P < 0.001]. More patients reported that they would prefer a telephone call for urgent advice (168, 54.9%). Conclusion Most patients interviewed were happy with their routine face-to-face appointment being switched to a telephone consultation. Of those interviewed, patients >50 years old were less likely than their younger counterparts to want telephone consultations in place of face-to-face appointments. Most patients in our study would prefer a telephone consultation for urgent advice. We must ensure that older patients and those in vulnerable groups who value in-person contact are not excluded. Telephone clinics in some form are here to stay in rheumatology for the foreseeable future.

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Structural variant detection in cancer genomes: computational challenges and perspectives for precision oncology

npj Precision Oncology ◽

10.1038/s41698-021-00155-6 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Ianthe A. E. M. van Belzen ◽

Alexander Schönhuth ◽

Patrick Kemmeren ◽

Jayne Y. Hehir-Kwa

Keyword(s):

Intratumor Heterogeneity ◽

Precision Oncology ◽

Single Nucleotide Variants ◽

Full Spectrum ◽

Single Nucleotide ◽

Sequencing Technologies ◽

Cancer Genomes ◽

Genomic Aberrations

AbstractCancer is generally characterized by acquired genomic aberrations in a broad spectrum of types and sizes, ranging from single nucleotide variants to structural variants (SVs). At least 30% of cancers have a known pathogenic SV used in diagnosis or treatment stratification. However, research into the role of SVs in cancer has been limited due to difficulties in detection. Biological and computational challenges confound SV detection in cancer samples, including intratumor heterogeneity, polyploidy, and distinguishing tumor-specific SVs from germline and somatic variants present in healthy cells. Classification of tumor-specific SVs is challenging due to inconsistencies in detected breakpoints, derived variant types and biological complexity of some rearrangements. Full-spectrum SV detection with high recall and precision requires integration of multiple algorithms and sequencing technologies to rescue variants that are difficult to resolve through individual methods. Here, we explore current strategies for integrating SV callsets and to enable the use of tumor-specific SVs in precision oncology.

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Prevalence of Wheat/Gluten-Related Disorders and Gluten-Free Diet in Paraguay: An Online Survey-Based Study

Nutrients ◽

10.3390/nu13020396 ◽

2021 ◽

Vol 13 (2) ◽

pp. 396

Author(s):

Noé Ontiveros ◽

Raúl Emilio Real-Delor ◽

José Antonio Mora-Melgem ◽

Carlos Eduardo Beltrán-Cárdenas ◽

Oscar Gerardo Figueroa-Salcido ◽

...

Keyword(s):

Latin American ◽

Weight Control ◽

Online Survey ◽

Adult Population ◽

Wheat Gluten ◽

Gluten Free Diet ◽

Gluten Free ◽

Questionnaire Response ◽

Face To Face ◽

Validated Questionnaire

Gluten-related disorders (GRDs) are increasing around the world, but their magnitude and relevance remain unknown in most Latin American countries. Thus, an online survey was conducted to estimate the prevalence of GRDs as well as adherence to a gluten-free diet (GFD) in Paraguayan adult population. There were 1058 individuals surveyed using a validated questionnaire (response rate of 93.9%). The self-reported prevalence rates were as follows (95% CI): gluten sensitivity (GS), 10.30% (8.53–12.29); non-celiac GS (NCGS), 5.19% (3.94–6.71); physician-diagnosed celiac disease (PD-CD), 3.11% (2.15–4.35); wheat allergy (WA), 2.07% (1.30–3.13); and adherence to GFD, 15.69% (13.55–18.02). Excluding CD, more women than men met the criteria for GRDs, adverse food reactions, and GFD (p < 0.05). Eight respondents reported the coexistence of NCGS with PD-CD and/or WA. Most cases on a GFD indicated medical/dietitian advice for following the diet (68.07%). Non-self-reported GS individuals indicated weight control (46.4%) and the notion that the GFD is healthier (20.2%) as the main motivations for following the diet. GRDs are not uncommon in Paraguayan adult population. It seems that there is awareness about GRDs and the GFD, but training about the diagnosis of GRDs is desirable because of the informed overlapping diagnoses of CD or WA with NCGS. Future studies involving face-to-face interviews are necessary.

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Identifying Aspects of Public Attitudes Toward Whole Genome Sequencing to Inform the Integration of Genomics into Care

Public Health Genomics ◽

10.1159/000515952 ◽

2021 ◽

pp. 1-12

Author(s):

Holly Etchegary ◽

Daryl Pullman ◽

Charlene Simmonds ◽

Zoha Rabie ◽

Proton Rahman

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Online Survey ◽

Public Attitudes ◽

Genetic Counselor ◽

Genomic Medicine ◽

Genomic Data ◽

Whole Genome ◽

The Public ◽

Genomic Test

Introduction: The growth of global sequencing initiatives and commercial genomic test offerings suggests the public will increasingly be confronted with decisions about sequencing. Understanding public attitudes can assist efforts to integrate sequencing into care and inform the development of public education and outreach strategies. Methods: A 48-item online survey was advertised on Facebook in Eastern Canada and hosted on SurveyMonkey in late 2018. The survey measured public interest in whole genome sequencing and attitudes toward various aspects of sequencing using vignettes, scaled, and open-ended items. Results: While interest in sequencing was high, critical attitudes were observed. In particular, items measuring features of patient control and choice regarding genomic data were strongly endorsed by respondents. Majority wanted to specify upfront how their data could be used, retain the ability to withdraw their sample at a later date, sign a written consent form, and speak to a genetic counselor prior to sequencing. Concerns about privacy and unauthorized access to data were frequently observed. Education level was the sociodemographic variable most often related to attitude statements such that those with higher levels of education generally displayed more critical attitudes. Conclusions: Attitudes identified here could be used to inform the development of implementation strategies for genomic medicine. Findings suggest health systems must address patient concerns about privacy, consent practices, and the strong desire to control what happens to their genomic data through public outreach and education. Specific oversight procedures and policies that are clearly communicated to the public will be required.

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Cross-border Life in an American Exclave: Point Roberts and the Canada–US Border

Borders in Globalization Review ◽

10.18357/bigr22202119617 ◽

2021 ◽

Vol 2 (2) ◽

pp. 38-51

Author(s):

Pierre-Alexandre Beylier

Keyword(s):

Qualitative Research ◽

Pacific Northwest ◽

Online Survey ◽

Border Studies ◽

Face To Face ◽

Cross Border ◽

Quantitative And Qualitative Research ◽

The Pacific ◽

Border Town ◽

Canadian City

By applying a theoretical framework based on different models proposed in border studies literature, this article analyzes the morphological, functional, institutional and identity characteristics that make Point Roberts—an American exclave in the Pacific Northwest—a “cross-border town”. Using an online survey and face-to-face interviews, the author combines both quantitative and qualitative research methods in order to examine the forces that link Point Roberts and the Canadian city of Delta that lies across the Canada–US border. This paper highlights the specificities of this unique geographic configuration as well the challenges that the border represents.

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