The effects of an online decision aid to support the reproductive decision-making process of genetically at risk couples-A pilot study.

Couples at risk of transmitting a genetic disease to their offspring may experience doubts about their reproductive options. This study examines the effects of an online decision aid (DA) on the (joint) reproductive decision-making process of couples (not pregnant at time of inclusion) at risk of transmitting a genetic disease to their offspring. The primary outcome is decisional conflict, and secondary outcomes are knowledge, realistic expectations, deliberation, joint informed decision-making, and decisional self-efficacy. These outcomes were measured with a pretest-posttest design: before use (T0), after use (T1), and 2 weeks after use (T2) of the decision aid (DA). Usability of the DA was assessed at T1. Paired sample t-tests were used to compute differences between baseline and subsequent measurements. The comparisons of T0-T1 and T0-T2 indicate a significant reduction in mean decisional conflict scores with stronger effects for participants with high baseline decisional conflict scores. Furthermore, use of the DA led to increased knowledge, improved realistic expectations, and increased levels of deliberation, with higher increase in participants with low baseline scores. Decision self-efficacy only improved for participants with lower baseline scores. Participants indicated that the information in the DA was comprehensible and clearly organized. These first results indicate that this online DA is an appropriate tool to support couples at risk of transmitting a genetic disease and a desire to have (a) child(ren) in their reproductive decision-making process.

Couples' experiences with expanded carrier screening: evaluation of a university hospital screening offer.

Preconception carrier screening offers couples the possibility to receive information about the risk of having a child with a recessive disorder. Since 2016, an expanded carrier screening (ECS) test for 50 severe autosomal recessive disorders has been available at Amsterdam Medical Center, a Dutch university hospital. This mixed-methods study evaluated the experiences of couples that participated in the carrier screening offer, including high-risk participants, as well as participants with a general population risk. All participants received genetic counselling, and pre- (n = 132) and post-test (n = 86) questionnaires and semi-structured interviews (n = 16) were administered. The most important reason to have ECS was to spare a future child a life with a severe disorder (47%). The majority of survey respondents made an informed decision (86%), as assessed by the Multidimensional Measure of Informed Choice. Among the 86 respondents, 27 individual carriers and no new carrier couples were identified. Turn-around time of the test results was considered too long and costs were perceived as too high. Overall, mean levels of anxiety were not clinically elevated. High-risk respondents (n = 89) and pregnant respondents (n = 13) experienced higher levels of anxiety before testing, which decreased after receiving the test result. Although not clinically significant, distress was on average higher for carriers compared to non-carriers (p < 0.0001). All respondents would opt for the test again, and 80.2% would recommend it to others. The results suggest that ECS should ideally be offered before pregnancy, to minimise anxiety. This study could inform current and future implementation initiatives of preconception ECS.

Preconception carrier screening for multiple disorders: evaluation of a screening offer in a Dutch founder population.

Technological developments have enabled carrier screening for multiple disorders. This study evaluated experiences with a preconception carrier screening offer for four recessive disorders in a Dutch founder population. Questionnaires were completed by 182 attendees pretesting and posttesting and by 137 non-attendees. Semistructured interviews were conducted with seven of the eight carrier couples. Attendees were mainly informed about the existence of screening by friends/colleagues (49%) and family members (44%). Familiarity with the genetic disorders was high. Knowledge after counseling increased (p < 0.001); however, still 9%, compared to 29% before counseling, wrongly mentioned an increased risk of having an affected child if both parents are carriers of different disorders. Most attendees (97%) recalled their test results correctly, but two couples reported being carrier of another disorder than reported. Overall, 63% felt worried while waiting for results but anxiety levels returned to normal afterwards. In all, 2/39 (5%) carriers felt less healthy. Screened individuals were very satisfied; they did not regret testing (97%) and would recommend testing to others (97%). The majority (94%) stated that couples should always have a pretest consultation, preferably by a genetic counselor rather than their general practitioner (83%). All carrier couples made reproductive decisions based on their results. Main reason for non-attendance was unawareness of the screening offer. With expanded carrier screening, adequately informing couples pretest and posttesting is of foremost importance. Close influencers (family/friends) can be used to raise awareness of a screening offer. Our findings provide lessons for the implementation of expanded carrier screening panels in other communities and other settings.

VAMP5 and VAMP8 are most likely not involved in primary open-angle glaucoma.

PURPOSE: To select and characterize novel POAG disease genes. On the basis of genetic position (GLC1B), expression in the optic nerve, and biochemical function (targeted membrane transport processes), we selected the human VAMP5 and VAMP8 (encoding vesicle-associated membrane proteins 5 and 8) as potential candidate disease genes for POAG. We subsequently analyzed whether or not sequence changes in VAMP5 or VAMP8 were implicated in POAG. METHODS: Genomic DNA samples from 90 POAG cases and 60 controls were screened by denaturing high performance liquid chromatography of fragments amplified by the polymerase chain reaction. Direct sequencing identified nucleotide changes. RESULTS: No nonsynonymous rare sequence variants were found in VAMP5 or VAMP8. In VAMP5, three previously identified and five new single nucleotide polymorphisms (SNPs) were found. In VAMP8, four known and two new SNPs were detected. All new SNPs did not appear to change gene function or alter gene splicing. No significant differences were found between the allele frequencies in POAG cases and controls. CONCLUSIONS: Our findings indicate that VAMP5 and VAMP8 are not involved in POAG in the Dutch population.

Targeted carrier screening for four recessive disorders: high detection rate within a founder population.

In a genetically isolated community in the Netherlands four severe recessive genetic disorders occur at relatively high frequency (pontocerebellar hypoplasia type 2 (PCH2), fetal akinesia deformation sequence (FADS), rhizomelic chondrodysplasia punctata type 1 (RCDP1), and osteogenesis imperfecta (OI) type IIB/III. Over the past decades multiple patients with these disorders have been identified. This warranted the start of a preconception outpatient clinic, in 2012, aimed at couples planning a pregnancy. The aim of our study was to evaluate the offer of targeted genetic carrier screening as a method to identify high-risk couples for having affected offspring in this high-risk subpopulation. In one year, 203 individuals (92 couples and 19 individuals) were counseled. In total, 65 of 196 (33.2%) tested individuals were carriers of at least one disease, five (7.7%) of them being carriers of two diseases. Carrier frequencies of PCH2, FADS, RCDP1, and OI were 14.3%, 11.2%, 6.1%, and 4.1% respectively. In individuals with a positive family history for one of the diseases, the carrier frequency was 57.8%; for those with a negative family history this was 25.8%. Four PCH2 carrier-couples were identified. Thus, targeted (preconception) carrier screening in this genetically isolated population in which a high prevalence of specific disorders occurs detects a high number of carriers, and is likely to be more effective compared to cascade genetic testing. Our findings and set-up can be seen as a model for carrier screening in other high-risk subpopulations and contributes to the discussion about the way carrier screening can be offered and organized in the general population.