Mode of delivery preference in prenatal genetic counseling between English- and Spanish-speaking patients at two US medical institutions.

Although Hispanic individuals are at an increased risk for various genetic conditions, they have lower uptake of genetic counseling and genetic testing. Virtual appointments have many advantages that may help Spanish-speaking patients access genetic services more readily. Despite these benefits, there are limitations that may make them less attractive options for these individuals. This study aimed to determine if satisfaction with genetic counseling or mode of delivery preference differs between English- and Spanish-speaking individuals who have had a virtual prenatal genetic counseling session. Participants were recruited from prenatal genetic counseling clinics at Indiana University Health and Eskenazi Hospital. A REDCap survey was sent to all eligible participants. Survey questions included mode of delivery preference for future genetic counseling sessions (virtual versus in-person), the validated Genetic Counseling Satisfaction Scale, and questions inquiring about the importance of various factors affecting mode of delivery preference. Spanish-speaking individuals preferred future visits to be in-person, while English-speaking individuals preferred future visits to be virtual (Fisher's exact p = 0.003). Several factors were associated with these preferences, including waiting time, ability to leave/take off work for an appointment, length of session, childcare arrangements, and people attending the appointment (all p < 0.05). Both language groups reported similar mean satisfaction with the genetic counseling provided during their previous virtual appointments (p = 0.51). This study found that certain aspects of virtual genetic counseling appointments make them less appealing to Spanish-speaking individuals. Making virtual genetic counseling appointments more appealing while continuing to offer in-person appointments may help Spanish-speaking individuals receive necessary genetics services. Continued research into disparities and barriers to telemedicine for Spanish-speaking patients is necessary to increase access to this service delivery model for genetic counseling.

Genetic counseling for advanced paternal age: A survey of genetic counselors' current practice.

Advanced paternal age (APA) has no formal definition, though many publications utilize the cutoff of fathers >40 years of age. The literature demonstrates an association between APA and certain conditions including de novo autosomal dominant disorders, birth defects, and neuropsychiatric conditions. This study surveyed 165 genetic counselors within the National Society of Genetic Counselors to assess their current approach to APA. t Tests, analysis of variance, logistic regression, and chi-squared tests were performed on quantitative data, and content analysis was applied to qualitative data. Although most respondents have discussed APA with a patient (88%), there was no consensus on what age cutoff constitutes APA: >40 (N = 53, 37.9%), >45 (N = 61, 43.6%), >50 (N = 24, 17.1%), or >55 (N = 2, 1.4%). Those who discussed APA were more likely to be prenatal counselors, see more patients per week, be board certified, or be familiar with current APA guidelines. Respondents agreed the literature supports the association of APA with deleterious outcomes (mean agreement = 8.2, median = 8 on a 1 = strongly disagree to 10 = strongly agree). Individuals who discussed APA and were board certified had higher agreement. Content analysis confirmed agreement that the literature supports an association between APA and deleterious outcomes (documented in responses from 31.5% of prenatal respondents, 17.8% others) but noted that available testing and screening options for associated conditions are limited (34.4% of prenatal respondents, 17.4% others). Prenatal and non-prenatal respondents reported similar agreement with the statement that APA is associated with deleterious outcomes. However, most non-prenatal respondents were unfamiliar with current guidelines (80%), and presumably as a result, were also less likely to discuss APA with their patients. Our study identified a need to disseminate information regarding APA and current guidelines to genetic counselors, particularly non-prenatal and those with less experience.

NIPT and Informed Consent: an Assessment of Patient Understanding of a Negative NIPT Result.

Since becoming clinically available in 2011, the use of noninvasive prenatal testing (NIPT) to screen for fetal aneuploidy has continued to increase. However, it has been questioned whether the education of patients undergoing NIPT consistently meets informed consent standards. We sought to evaluate patients' basic understanding of NIPT, such as conditions assessed and accuracy. In addition, we investigated patient self-assessment of NIPT knowledge and satisfaction with the testing process. We distributed an anonymous paper survey to pregnant women during prenatal visits following a negative NIPT result. The survey assessed patient NIPT knowledge, gathered pregnancy-specific and demographic information, and allowed respondents to rank their basic understanding of NIPT and provide written feedback about the testing process. A total of 95 completed and 3 partially completed surveys were returned. Participants scored lowest on knowledge questions involving whether a negative NIPT result ensures a healthy baby or eliminates the possibility of Down syndrome. Most perceived themselves to have a good basic understanding of NIPT and two-thirds of the written feedback proposed no changes to NIPT administration. Overall, most patients appear satisfied with their understanding of NIPT and the testing process, yet they may not fully appreciate the limitations of this screening method.

Prenatal diagnosis of Carpenter syndrome: looking beyond craniosynostosis and polysyndactyly.

Carpenter syndrome is an autosomal recessive disorder comprising craniosynostosis, polysyndactyly, and brachydactyly. It occurs in approximately 1 birth per million. We present a patient with Carpenter syndrome (confirmed by molecular diagnosis) who has several unique and previously unreported manifestations including a large ovarian cyst and heterotaxy with malrotation of stomach, intestine, and liver. These findings were first noted by prenatal ultrasound and may assist in prenatally diagnosing additional cases of Carpenter syndrome.

Genetic counselors' experience with cell-free fetal DNA testing as a prenatal screening option for aneuploidy.

First identified in 1997, cell-free fetal DNA (cffDNA) has just recently been used to detect fetal aneuploidy of chromosomes 13, 18, and 21, showing its potential to revolutionize prenatal genetic testing as a non-invasive screening tool. Although this technological advancement is exciting and has certain medical applications, it has been unclear how it will be implemented in a clinical setting. Genetic counselors will likely be instrumental in answering that question, but to date, there is no published research regarding prenatal counselors' implementation of and experiences with cffDNA testing. We developed a 67 question survey to gather descriptive information from counselors regarding their personal opinions, experiences, thoughts, and concerns regarding the validity, usefulness, and implementation of this new technology. A total of 236 individuals completed a portion of the survey; not all respondents answered all questions. Qualitative questions complemented quantitative survey items, allowing respondents to voice their thoughts directly. Results indicate that counselors value cffDNA testing as a screening option but are concerned regarding how some obstetricians and patients make use of this testing. Further results, discussion, and practice implications are presented.

OBGYN providers' lack of knowledge and management of genetic risks due to advanced paternal age underscore the need for updated practice guidance.

The objective of this pilot study was to characterize healthcare professionals' knowledge of advanced paternal age (APA), the associated risks, as well as current clinical practices regarding APA. Our study utilized an online survey that questioned providers who see children with genetic conditions and patients who are or may become pregnant regarding demographic information, APA knowledge, APA guideline familiarity, and their clinical practices. A total of 67 providers responded to the survey. We had responses from 54 physician participants in the specialties of medical genetics (GEN), maternal fetal medicine (MFM), and obstetrics and gynecology (OBGYN). OBGYN, but not MFM, reported significantly lower agreement that current data supports an association between APA and certain genetic diseases compared to GEN. Furthermore, OBGYN were less likely to identify established risks associated with APA and more likely to incorrectly identify unestablished risks compared to GEN and MFM. Regardless of specialty, the majority of physicians were unfamiliar with the most recently published APA guidelines. This study revealed a desire for more information regarding APA risks and management among our participants. Our data suggest that GEN, MFM, and OBGYN would benefit from updated and more visible guidelines regarding APA. Additionally, OBGYN consistently showed knowledge gaps and misconceptions regarding the risks of APA. Targeted educational or guidance materials regarding APA may also be beneficial for OBGYNs.

Genetic counselors' perceived responsibilities regarding reproductive issues for patients at risk for Huntington disease.

Research indicates that health care professionals' attitudes may affect patients' decisions regarding prenatal Huntington Disease testing, but few studies have sampled genetic counselors. In this qualitative study, genetic counselors described their experiences counseling individuals at risk for HD regarding reproductive decision-making. Five major research questions were investigated: 1) What are genetic counselor responsibilities? 2) What issues arise for patients and counselors? 3) How do counselors reconcile prenatal testing with presymptomatic testing? 4) To what extent are counselors' initial expectations of at-risk patients' beliefs and behaviors met? and 5) What advice would counselors offer to novice practitioners about working with this patient population? Fifteen genetic counselors experienced in counseling individuals at risk for HD participated in a semi-structured phone interview that yielded several themes. For example, participants identified their primary responsibility as information provision; less prevalent were psychosocial support and facilitating decision making. The most common ethical challenge was testing prenatally for HD which also results in presymptomatic testing of minors. Participants were divided about how directive to be in response to this ethical issue and about termination of a gene positive pregnancy.

Conserved properties of HP1(Hsalpha).

Heterochromatin protein 1 Hsalpha (HP1(Hsalpha)) is one of three human proteins that share sequence similarity with Drosophila HP1. HP1 proteins are enriched at centric heterochromatin and play a role in chromatin packaging and gene regulation. In humans, HP1(Hsalpha) is down-regulated in highly invasive/metastatic breast cancer cells, compared to poorly invasive/non-metastatic breast cancer cells. To gain insight into this differential regulation, we have cloned the HP1(Hsalpha) gene and characterized its genomic region. HP1(Hsalpha) is located on human chromosome 12q13.13, 589 bp upstream of the divergently transcribed hnRNPA1 gene. Analysis of the promoter region revealed that differential regulation of HP1(Hsalpha) between the two types of breast cancer cells is lost upon mutation of an USF/c-myc transcription factor binding site located 172 bp upstream of the predicted HP1(Hsalpha) transcription start site. These findings provide insights into the down-regulation of HP1(Hsalpha) in highly invasive/metastatic breast cancer cells. To examine the functional properties of HP1(Hsalpha), experiments were performed using Drosophila melanogaster as a genetic system. When human HP1(Hsalpha) was expressed in transgenic Drosophila, silencing of reporter genes inserted at centric and telomeric locations was enhanced. Furthermore, expression of HP1(Hsalpha) rescued the lethality of homozygous Su(var)2-5 mutants lacking HP1. Taken together, these results demonstrate the participation of HP1(Hsalpha) in silent chromatin formation and that HP1(Hsalpha) is a functional homologue of Drosophila HP1.

Domains of heterochromatin protein 1 required for Drosophila melanogaster heterochromatin spreading.

Centric regions of eukaryotic genomes are packaged into heterochromatin, which possesses the ability to spread along the chromosome and silence gene expression. The process of spreading has been challenging to study at the molecular level due to repetitious sequences within centric regions. A heterochromatin protein 1 (HP1) tethering system was developed that generates "ectopic heterochromatin" at sites within euchromatic regions of the Drosophila melanogaster genome. Using this system, we show that HP1 dimerization and the PxVxL interaction platform formed by dimerization of the HP1 chromo shadow domain are necessary for spreading to a downstream reporter gene located 3.7 kb away. Surprisingly, either the HP1 chromo domain or the chromo shadow domain alone is sufficient for spreading and silencing at a downstream reporter gene located 1.9 kb away. Spreading is dependent on at least two H3K9 methyltransferases, with SU(VAR)3-9 playing a greater role at the 3.7-kb reporter and dSETDB1 predominately acting at the 1.9 kb reporter. These data support a model whereby HP1 takes part in multiple mechanisms of silencing and spreading.