Experience Of Genetic Testing Research Articles

Investigation of patients with childhood epilepsy in single center: Comprehensive genetic testing experience.

Epilepsy is a common multifactorial neurological disease usually diagnosed during childhood. In this study, we present the contribution of consecutive genetic testing to the genetic diagnostic yield of childhood epilepsy. In 100 children (53 female, 47 male) with epilepsy, targeted sequencing (TS) and clinical exome sequencing (CES) were performed. All cases (n= 100) included in the study were epilepsy patients. In addition, we investigated the genetic diagnosis rates according to the associated co-occurring findings (including developmental delay/intellectual disability, brain malformations, macro-/microcephaly, and dysmorphic features). The overall diagnostic rate in this study was 33% (n= 33 patients). We identified 11 novel variants in WDR45, ARX, PCDH19, SCN1A, CACNA1A, LGI1, ASPM, MECP2, NF1, TSC2, and CDK13. Genetic diagnosis rates were as follows: cases with developmental delay/intellectual disability 38.7% (24/62) and without developmental delay/intellectual disability 23.6% (9/38); cases with brain malformations 46.8% (15/32) and without brain malformations 25% (16/64); cases with macro-/microcephaly 50% (6/12) and without macro-/microcephaly 28.4% (25/88); and cases with dysmorphic features 48.2% (14/29) and without dysmorphic features 23.9% (17/71). Genotype-phenotype correlation is even more important in diseases such as epilepsy, which include many genes and variants of these genes in etiopathogenesis. We presented the clinical findings of the cases carrying 11 novel variants in detail, including dysmorphic features, accompanying neurodevelopmental disorders, EEG results, and brain MRI results.

Experiences of predictive genetic testing in inherited motor neuron disease: Findings from a qualitative interview study

Experiences of predictive genetic testing in inherited motor neuron disease: Findings from a qualitative interview study

Genetic Testing Experiences of People Living with Inherited Retinal Degenerations: Results of a Global Survey

Introduction: Obtaining a genetic diagnosis via genetic testing (GT) is a fundamental step in determining the eligibility of a patient to be enrolled in emerging clinical trials and research studies. Besides, the knowledge of genetic outcome allows patients to plan for significant life choices. However, critical barriers exist to an equitable access to genetic services globally. The objective of this study was to explore patient experiences while seeking genomic services for inherited retinal degenerations (IRDs). Methods: An online survey was designed based on a focus group conducted by Retina International and including people affected by IRDs and their families living in different regions around the world. The survey was then circulated to 43 Retina International member organisations globally via email newsletters and social networks. The survey involved questions in relation to the accessibility, affordability, and timeliness of genomic services for IRDs as well as patient perceived awareness of genomic services for IRDs among healthcare professionals. Results: A total of 410 respondents (IRD patients and caregivers) from over 30 countries across all continents responded to the survey. A considerable number of the patients had to go through a long and arduous journey to access GT and counselling services, wherein 40% had to visit more than 5 physicians, 27% had to visit more than 5 clinics, and 57% had to wait for more than 3 years before obtaining a genetic diagnosis. Furthermore, 46% of respondents reported not receiving genetic counselling prior to undergoing GT, and 39% reported not receiving genetic counselling after undergoing GT. Over 3/4th of the participants reported that they did not have to pay for their genomic services for IRDs. Thirty-seven percent of the respondents reported that their eye care professionals (ECPs) were either not aware of GT, remained neutral, or did not encourage them to undergo GT. Conclusion: Patients with IRDs do not have equitable access to best practice GT and counselling services. Greater awareness and training regarding IRDs and the benefits of GT and genetic counselling for patients and families are needed among ECPs. A best practice model on access to genomic services for IRDs is required.

Perception of genomic newborn screening among peripartum mothers.

Advances in genomic technology have generated possibilities for expanding newborn screening from traditional procedures to genomic newborn screening (gNBS). However, before the implementation of gNBS, it is crucial to address various aspects, including parental attitudes, at the national level. With this aim, we analyzed the attitudes and expectations of Slovenian peripartum mothers regarding gNBS and the acceptability of its implementation into the Slovenian health system. A questionnaire-based study was conducted on a convenience sample of 1136 peripartum mothers (a response rate of 84.1%) in a hospital setting in Slovenia. We measured participants' level of general genetic knowledge, motivation to undergo gNBS, attitude toward its benefits and drawbacks, willingness to participate financially, and factors that would influence their decision to undergo gNBS. Most participants exhibited a positive attitude (83.2%) and were motivated to undertake gNBS (63.4%). They were willing to share genetic data and also contribute to the testing costs. Mothers with better genetic literacy and higher education level, and those with the familial genetic testing experiences were more supportive of gNBS. However, several emotional and socio-ethical concerns were raised regarding how the genetic information would influence family and social life.

Experiences of Family Communication and Cascade Genetic Testing for Hereditary Cancer in Medically Underserved Populations-A Qualitative Study.

This study of intrafamilial communication and cascade genetic testing experiences of patients with hereditary cancer and their relatives from diverse, medically underserved populations identified relatives' perceived susceptibility to hereditary cancer risks, distress, and fear as frequent reactions and barriers to testing. These results may inform future hereditary cancer prevention efforts.

SURvey of Surgeon's and Physician's experiences of GEnetic testing in patients with Familial Endocrine Syndromes: SurGe in UK and Abroad

SURvey of Surgeon's and Physician's experiences of GEnetic testing in patients with Familial Endocrine Syndromes: SurGe in UK and Abroad

"Out of the blue": A qualitative study exploring the experiences of women and next of kin receiving unexpected results from BRA-STRAP research gene panel testing.

In the genomic era, the availability of gene panel and whole genome/exome sequencing is rapidly increasing. Opportunities for providing former patients with new genetic information are also increasing over time and recontacting former patients with new information is likely to become more common. Breast cancer Refined Analysis of Sequence Tests-Risk And Penetrance (BRA-STRAP) is an Australian study of individuals who had previously undertaken BRCA1 and BRCA2 genetic testing, with no pathogenic variants detected. Using a waiver of consent, stored DNA samples were retested using a breast/ovarian cancer gene panel and clinically significant results returned to the patient (or next of kin, if deceased). This qualitative study aimed to explore patient experiences, opinions, and expectations of recontacting in the Australian hereditary cancer setting. Participants were familial cancer clinic patients (or next of kin) who were notified of a new pathogenic variant identified via BRA-STRAP. In-depth, semi-structured interviews were conducted approximately 6 weeks post-result. Interviews were transcribed verbatim and analyzed using an inductive thematic approach. Thirty participants (all female; average age = 57; range 36-84) were interviewed. Twenty-five were probands, and five were next of kin. Most women reported initial shock upon being recontacted with unexpected news, after having obtained a sense of closure related to their initial genetic testing experiences and cancer diagnosis. For most, this initial distress was short-lived, followed by a process of readjustment, meaning-making and adaptation that was facilitated by perceived clinical and personal utility of the information. Women were overall satisfied with the waiver of consent approach and recontacting process. Results are in line with previous studies suggesting that patients have positive attitudes about recontacting. Women in this study valued new genetic information gained from retesting and were satisfied with the BRA-STRAP recontact model. Practice implications to facilitate readjustment and promote psychosocial adaptation were identified.

Perspectives of carriers of X-linked retinal diseases on genetic testing and gene therapy: A global survey.

Female carriers of X-linked inherited retinal diseases (IRDs) are burdened with potentially passing their disease-causing variant to future generations, as well as exhibiting signs of retinal disease themselves. This study aimed to investigate carriers' experiences of genetic testing, emotions relating to having affected children, and their knowledge regarding genetic testing and gene therapy. An online survey was advertised to self-identified carriers worldwide. Two hundred and twenty-eight carriers completed the survey with mean age of 51 years (SD ± 15.0). A majority of respondents resided in the United States of America (51%), Australia (19%), and the United Kingdom (14%). Most carriers identified with feelings of guilt (70%), concern (91%), and anxiety (88%) for their child. Female carriers who had given birth to children had significantly greater gene therapy knowledge compared to carriers who had not (p < 0.05). Respondents agreed that their eyecare provider and general practitioner helped them understand their condition (63%), however, few carriers reported receiving psychological counselling (9%) or family planning advice (5%). Most respondents (78%) agreed that gene therapy should be available to carriers. This study emphasises the importance of providing appropriate counselling to female carriers and illustrates the motivation of many to participate in emerging treatment options, such as gene therapy.

Assessing pharmacogenomic literacy in China through validation of the Chinese version of the Minnesota Assessment of Pharmacogenomic Literacy.

Pharmacogenomics (PGx) implementation into clinical care is rapidly increasing in China. However, the extent to which the public understands PGx testing and important knowledge domains requiring patient education or counseling remains unclear. To address this, we created and validated the Chinese version of the Minnesota Assessment of Pharmacogenomic Literacy (MAPL-CTM ). The MAPL-C was developed by translating the English MAPL to Chinese following cross-cultural translation guidelines. An online survey validated the MAPL-C and assessed Chinese individuals' PGx literacy. Validation analyses were performed and associations of PGx literacy with participants' characteristics were quantified. Of 959 high-quality responses, the majority of respondents were Han Chinese (96.3%), men (54.5%), aged 18-29 years (70.9%), residing in China (97.3%), and had received college or higher education (95.0%). Out of 15 starting items developed to query specific predefined knowledge domains, two uninformative items were excluded, resulting in a 13-item MAPL-C. Chinese participants' MAPL-C performance was best explained by a three-factor model, encompassing PGx concepts and function, testing limitations, and privacy. Higher MAPL-C performance was associated with younger age, higher education, and previous genetic testing experience. Correct response rates for questions related to testing limitations were lower than those in other domains. The creation and validation of the MAPL-C fills a gap in determining PGx knowledge among Chinese speakers, quantifying PGx literacy within a Chinese cohort, and identifying response patterns and knowledge gaps. The MAPL-C can be useful in clinical practice to guide patient counseling, assess PGx education interventions, and quantify PGx knowledge in relation to outcomes in research studies involving Chinese participants.

Genetic testing decision-making experiences within families of colorectal cancer patients: A qualitative study

PurposeGenetic testing is the gold standard for the diagnosis of hereditary colorectal cancer syndromes but is currently inadequate and nonideal. The decision-making processes regarding genetic testing are even less well known. The present study aims to explore the decision-making experience of genetic testing for colorectal cancer patients and their family members. MethodA descriptive qualitative study was employed. Data were collected using individual semi-structured interviews with 5 colorectal cancer patients and 20 family members from November 2020 to April 2021. Interviews were transcribed and analysed using inductive content analysis. ResultsFour categories were identified: 1) the source of information for genetic testing, 2) the differentiated attitudes towards genetic testing, 3) genetic testing decisional needs, and 4) the factors influencing genetic testing decision-making. Colorectal cancer patients and their families engaged in two distinct pathways to genetic testing decisions: direct decision-making and indirect decision-making. Throughout these processes, due to the limited source of information, they had information needs that were met and facilitated genetic testing decision-making. ConclusionsColorectal cancer patients and family members need knowledge related to genetic testing, but they have limited access to information, which prevents them from making informed decisions. Providing decision aid interventions and informational support are significant steps towards addressing the support needs of this population.

Experience in prenatal genetic testing and reproductive decision-making for monogenic disorders from a single tertiary care genetics clinic in a low-middle income country

ObjectivesExplore health-care seeking behaviour among couples with pregnancies at-risk of monogenic disorders and compare time duration for obtaining Prenatal Genetic Test (PGT) results based on (i) amniocentesis and Chorionic Villus Sampling (CVS) (ii) in-house testing and out-sourced testing. Report the spectrum of monogenic disorders in our cohort.MethodsMedical records of women consulting prenatal genetic counselling clinic at Aga Khan University Hospital, Karachi from December-2015 to March-2021 with history of miscarriage or a monogenic disorder in previous children were reviewed.ResultsForty-three pregnancies in 40 couples were evaluated, 37(93%) were consanguineous. Twenty-five (63%) couples consulted before and 15(37%) after conception. Thirty-one (71%) pregnancies underwent CVS at the mean gestational age of 13-weeks and 6-days ± 1-week and 3-days and amniocentesis at 16-weeks and 2-days ± 1-week and 4-days. PGT for 30 (70%) pregnancies was outsourced. The mean number of days for in-house PGT was 16.92 ± 7.80 days whereas for outsourced was 25.45 ± 7.7 days. Mean duration from procedure to PGT result was 20.55 days after CVS compared to 28.75 days after amniocentesis. Eight (18%) fetuses were homozygous for disease-causing variant for whom couples opted for termination of pregnancy (TOP). Twenty-six monogenetic disorders were identified in 40 families.ConclusionProactive health-care seeking behaviour and TOP acceptance is present amongst couples who have experienced a genetic disorder.

Knowledge, attitudes and experiences of genetic testing for autism spectrum disorders among caregivers, patients, and health providers: A systematic review.

Several genetic testing techniques have been recommended as a first-tier diagnostic tool in clinical practice for diagnosing autism spectrum disorder (ASD). However, the actual usage rate varies dramatically. This is due to various reasons, including knowledge and attitudes of caregivers, patients, and health providers toward genetic testing. Several studies have therefore been conducted worldwide to investigate the knowledge, experiences, and attitudes toward genetic testing among caregivers of children with ASD, adolescent and adult ASD patients, and health providers who provide medical services for them. However, no systematic review has been done. To systematically review research on knowledge, experiences, and attitudes towards genetic testing among caregivers of children with ASD, adolescent and adult ASD patients, and health providers. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and searched the literature in three English language databases (PubMed, Web of Science, and PsychInfo) and two Chinese databases (CNKI and Wanfang). Searched literature was screened independently by two reviewers and discussed when inconsistency existed. Information on characteristics of the study, characteristics of participants, and main findings regarding knowledge, experience, and attitudes of caregivers of children with ASD, adolescent and adult ASD patients, and health providers concerning ASD genetic testing were extracted from included papers into a charting form for analysis. We included 30 studies published between 2012 and 2022 and conducted in 9 countries. Most of the studies (n = 29) investigated caregivers of children with ASD, one study also included adolescent and adult patients, and two covered health providers. Most (51.0%-100%) of the caregivers/patients knew there was a genetic cause for ASD and 17.0% to 78.1% were aware of ASD genetic testing. However, they lacked full understanding of genetic testing. They acquired relevant and necessary information from physicians, the internet, ASD organizations, and other caregivers. Between 9.1% to 72.7% of caregivers in different studies were referred for genetic testing, and between 17.4% to 61.7% actually obtained genetic testing. Most caregivers agreed there are potential benefits following genetic testing, including benefits for children, families, and others. However, two studies compared perceived pre-test and post-test benefits with conflicting findings. Caregivers concerns included high costs, unhelpful results, negative influences (e.g., causing family conflicts, causing stress/risk/pain to children etc.) prevented some caregivers from using genetic testing. Nevertheless, 46.7% to 95.0% caregivers without previous genetic testing experience intended to obtain it in the future, and 50.5% to 59.6% of parents previously obtaining genetic testing would recommend it to other parents. In a single study of child and adolescent psychiatrists, 54.9% of respondents had ordered ASD genetic testing for their patients in the prior 12 mo, which was associated with greater knowledge of genetic testing. Most caregivers are willing to learn about and use genetic testing. However, the review showed their current knowledge is limited and usage rates varied widely in different studies.

Exploring the impact of the reclassification of a hereditary cancer syndrome gene variant: emerging themes from a qualitative study

The complexity of genetic variant interpretation means that a proportion of individuals who undergo genetic testing for a hereditary cancer syndrome will have their test result reclassified over time. Such a reclassification may involve a clinically significant upgrade or downgrade in pathogenicity, which may have significant implications for medical management. To date, few studies have examined the psychosocial impact of a reclassification in a hereditary cancer syndrome context. To address this gap, semi-structured telephone interviews were performed with eighteen individuals who had a BRCA1, BRCA2 or Lynch syndrome-related (MLH1, MSH2, MSH6 or PMS2) gene variant reclassified. The interviews were analysed utilising an inductive, qualitative approach and emergent themes were identified by thematic analysis. Variable levels of recall amongst participants were found. Common motivations for initial testing included a significant personal and/or family history of cancer and a desire to “find an answer”. No individual whose uncertain result was upgraded reported negative psychosocial outcomes; most reported adapting to their reclassified result and appraised their genetic testing experience positively. However, individuals whose likely pathogenic/pathogenic results were downgraded reported feelings of anger, shock and sadness post reclassification, highlighting that additional psychosocial support may be required for some. Genetic counselling issues and recommendations for clinical practice are outlined.

Women’s Metaphors About BRCA Gene Testing and How They Can Inform Health Communication Theory and Practice

ABSTRACT Genetic testing can detect whether an individual carries a harmful variant in the BRCA1 or BRCA2 (Breast Cancer 1 or 2) gene which, if present, drastically increases a woman’s risk for breast and ovarian cancer. The experience of BRCA gene testing can be an emotionally laden process yielding significant uncertainty. In this study, we examined women’s experiences of BRCA gene testing by exploring how participants communicatively framed and made sense of this process through the use of metaphors. Comparing uncertain and unfamiliar experiences to familiar references through metaphor can help people in challenging health-related situations with sense-making and communicating complex emotions. Furthermore, metaphors can be employed as a therapeutic tool by health care professionals, but their use has not often been studied regarding experiences of genetic testing, including BRCA gene testing. We conducted in-depth interviews with 42 women who have undergone BRCA gene testing (regardless of results), and analyzed data using constant comparative techniques. Eight categories of metaphors that women used surrounding BRCA gene testing were evident in the data, including those related to (a) knowledge is power; (b) gambling; (c) a journey; (d) a rollercoaster; (e) battle, disaster, or wreckage; (f) Pandora’s box or a can of worms; (g) doom and gloom; and (h) the release or placing of a weight. Results enhance our understanding of women’s experiences related to the uncertainty-inducing process of BRCA gene testing and lead to valuable theoretical implications and practical recommendations, including regarding the potential use of metaphors in patient-provider communication about BRCA genetic risk.

The Genetic Testing Experience of Individuals with Parkinson's Disease.

The perspective and experiences of individuals with Parkinson's disease (PD) regarding genetic testing is limited. To determine if anticipated benefits and negative consequences of genetic testing noted in prior studies have occurred in a surveyed group of patients with PD and to identify reasons why some individuals with PD have not had testing. Individuals were surveyed from 22 support/advocacy groups throughout the US. Information about patient demographics and genetic testing were assessed, along with the consequences experienced after testing or anticipated by those who have not had testing. Descriptive statistics, Pearson correlation coefficient, ANOVA, and independent sample t-test were utilized for data analysis. Of the genetic testing group (n= 78), most received testing through a research study (44.9%) or a Direct-to-Consumer company (46.2%). Most did not meet with a genetic counselor before (87.2%) or after testing (64.1%). Fewer positive and fewer negative consequences were reported after testing compared to the consequences anticipated by those who have not undergone testing (P< 0.001, all comparisons). Of the non-genetic testing group (n= 166), 49.4% did not undergo testing because they were not aware it was available and 38.0% because their doctor did not offer it. Findings demonstrate the need for providers to have genetic testing discussions with PD patients, who may otherwise seek testing via Direct-to-Consumer companies or be unaware it is available. Collaborations with genetic counselors trained in providing anticipatory guidance may assist patients in forming more realistic expectations regarding the consequences experienced after genetic testing for PD.

Using semi‐structured interview to develop a tailored psychological intervention for individuals at risk for familial Frontotemporal dementia

AbstractBackgroundFrontotemporal dementia is genetic in around a third of cases. Issues such as high penetrance, heterogenous symptoms and unpredictable onset may cause significant challenges for those at‐risk. Few studies have evaluated this experience and no interventions have been designed to support this group. Therefore, investigation of the at‐risk experience is required to ensure an intervention that is tailored to and appropriate for the target population, as outlined in stage 0 of the NIH stage model for Behavioural Intervention Development.MethodParticipants were individuals enrolled in UK GENFI, at‐risk of MAPT, GRN and C9orf72 mutations. Participants included those with unknown genetic status, asymptomatic mutation carriers and non‐carriers. 71 participants completed questionnaires, including GAD‐7 and PHQ‐9 measures, and the Genetic Psychosocial Risk Instrument. 16 qualitative interviews were conducted, regarding feelings experienced throughout the at‐risk journey, support needs and the genetic testing experience. An inductive approach to thematic analysis was used. Themes were then utilised to form the content of the intervention and guide design.ResultThere were no significant differences between genetic groups on GAD‐7, PHQ‐9 and GPRI measures, however 52% participants met the GPRI threshold for referral for psychosocial intervention.Key themes included: 1) Emotions experienced, 2) How risk influences how you live your life, 3) Coping, 4) Support wanted, 5) Barriers and facilitators, and 6) The importance of understanding the specific difficulties. Many participants expressed a desire for tailored psychological support facilitated by “someone who understands”. Intervention design The intervention applies principles largely derived from the Acceptance and Commitment Therapy model and has a blended design comprising of online sessions over eight weeks, with psychoeducational videos and three face‐to‐face sessions. There are seven to ten modules depending on the individual’s genetic status including: anxiety and low mood, rumination, survivor guilt, concern about symptom onset and uncertainty. A pilot study is currently underway and will be completed by April 2022.ConclusionLiving at‐risk of familial FTD is challenging, often requiring additional support therefore this work demonstrates the importance of NIH stage 0 research in intervention development. Future research should further explore the effectiveness of tailored interventions in at‐risk familial FTD.

Genetic Diagnosis of Inborn Errors of Immunity in an Emerging Country: a Retrospective Study of 216Moroccan Patients.

Genetic testing provides great support to validate the clinical diagnosis of inborn errors of immunity (IEI). However, the high cost and advanced technology make these tests inaccessible to a large proportion of patients in low-income countries. In the present study, we aim to evaluate the Moroccan experience in genetic testing and to report the main molecular features and difficulties encountered in genetic diagnosis. We performed a multi-center retrospective analysis of all patients with a molecular diagnosis and registered in the national registry between 2010 and 2022. To estimate the impact of the newly identified mutations, we calculated the Combined Annotation Dependent Depletion (CADD) score and the mutation significance cutoff (MSC) for each variant. A total of 216 (29%) patients received a genetic diagnosis out of 742 patients with IEI included in the registry. All genetic tests were performed in the context of thesis projects (40%) or international collaborations (60%). A set of 55 genetic defects were identified, including 7 newly reported: SNORA31, TBX21, SPPL2A, TYK2, RLTPR, ZNF341, and STAT2 GOF. Genetic diagnoses were more frequent in the defects of innate and intrinsic immunity with a percentage of 78%, while antibody deficiencies had a lower frequency with a percentage of 17.5%. Only one genetic diagnosis has been made in the complement deficiency group. The most commonly used molecular techniques were Sanger sequencing (37%) followed by targeted gene sequencing (31%). The thesis projects and collaborations were beneficial as they allowed us to provide a definitive genetic diagnosis to 29% of the patients and to contribute to the identification of new genetic defects and mutations. These results offer insight into the progress made in genetic diagnoses of IEI in Morocco, which would provide a baseline for improving the clinical management of patients with IEI.

Development of a web-based, theory-guided narrative intervention for women at elevated risk for breast cancer

ObjectiveTo describe the development of a web-based, theory-guided narrative intervention that replaces conventional pre-test genetic counseling for women at elevated breast cancer risk. MethodsWe used an iterative process that was guided by health behavior theory and feedback from multiple stakeholder groups including: 1) content input from genetic experts; 2) study team input; 3) review of video storyboards, video example, study logo, recruitment materials, post-test patient preference counseling survey, and additional study surveys; 4) video series development; and 5) intervention review and finalization of study-related materials. ResultsThe intervention is patient-centered providing convenience and an opportunity for an individual’s preferences for post-test counseling delivery. The intervention’s efficacy is being determined in a randomized controlled trial compared to conventional genetic counseling for adherence to recommended guidelines and changes in knowledge, perception of breast cancer risk, breast cancer-specific worry, and satisfaction with counseling. ConclusionIf efficacious, the intervention may improve the delivery of the genetic testing and counseling process, inform best practices, and reduce the genetic counseling workforce burden. Practice ImplicationsThe developed intervention has the potential to improve the genetic testing and counseling experience for women at elevated risk for breast cancer, inform best practices, and reduce genetic counseling workforce burden.

Genetics professionals are key to the integration of genetic testing within the practice of frontline clinicians

PurposeGenetic tests have become widely available. We sought to understand the use of genetic tests in the practice of frontline clinicians within the United States Department of Veterans Affairs (VA). MethodsWe administered a web-based survey to clinicians at 20 VA facilities. Physicians, nurse practitioners, physician assistants, and pharmacists were eligible. We excluded genetics providers and clinicians not seeing patients. We used multiple logistic regression to evaluate the associations between clinician characteristics and experience with genetics. ResultsThe response rate was 11.3% (1207/10,680) and of these, 909 respondents were eligible. Only 20.8% of the respondents reported feeling prepared to use genetic tests and 13.0% of the respondents were currently ordering genetic tests; although, it was usually only 1 or 2 a year. Delivery of genetic tests without involving genetics providers was preferred by only 7.9% of the respondents. Characteristics positively associated with currently ordering genetic tests included practice in clinical and research settings, believing improving genetics knowledge could alter their practice, feeling prepared to use genetic tests, and referral of at least 1 patient to genetics in the past year. ConclusionMost VA clinicians don’t feel prepared to use genetic tests. Those with genetic testing experience are more likely to consult genetics providers. The demand for genetics providers should increase as frontline clinicians use genetic tests in their practice.

The cholestatic infant: updates on diagnosis and genetics.

Cholestasis in infants can indicate a serious hepatobiliary disease and requires timely assessment, diagnosis and intervention to prevent progression to serious liver decompensation. This report aims to highlight recently published studies regarding diagnosis and treatment of cholestasis in infants. The evaluation of neonatal cholestasis can be challenging, requiring the assessment of a broad differential diagnosis in timely fashion. The Italian Society of pediatric gastroenterology, hepatology, and nutrition position paper on the evaluation of neonatal cholestasis is reviewed and compared to other published guidelines. In biliary atresia, the most time-sensitive of these diagnoses, serum matrix metalloproteinase-7 was studied in Japanese infants with biliary atresia with excellent diagnostic performance characteristics. Genetic testing panels are an increasingly used tool to help identify causes of cholestasis. An American experience of genetic testing in large cohort of infants identified a definite or possible genetic diagnosis in 11% of cholestatic infants. In the treatment of prutitus in Alagille syndrome and progressive familial intrahepatic cholestasis the clinical studies of two newly Food and Drug Administration approved ileal bile acid transport inhibitors are discussed. New information on the prevalence of cytomegalovirus and idiopathic cholestasis as other etiologies of infant cholestasis is also reviewed. Lastly, new insight on potential maternal microbiome regulation on biliary disease in neonates on experimental biliary atresia models is discussed. Cholestasis in infants requires timely diagnosis and intervention. There are exciting new diagnostic and treatment options now being studied which could help minimize the likelihood of advanced liver disease and development of serious complications.