Reproductive Genetic Counseling Research Articles

Neurologists’ understanding of reproductive medicine options for genetic forms of motor neuron disease

Objectives To examine the knowledge, confidence and practice of motor neuron disease (MND) clinicians toward discussing reproductive options with people who carry a causal variant in an MND gene (both clinically affected and asymptomatic). Methods An online cross-sectional survey was distributed nationwide to UK MND clinicians and clinical geneticists and genetic counselors. The survey assessed respondents’ understanding on reproductive medicine techniques; their confidence in discussing reproductive medicine options and their access to information resources. Results Seventy six clinicians responded to the online survey (45 neurology clinicians and 31 clinical geneticists). MND clinicians had limited knowledge and low confidence in discussing reproductive medicine options. Geneticists were more likely to carry out reproductive genetic counseling with very few MND clinicians reporting undertaking these discussions. Further, 57% of the 45 MND clinicians surveyed reported to have never made a referral for reproductive genetic counseling. Multiple barriers to offering reproductive counseling or referral were identified including a lack of knowledge, lack of awareness of the different options, lack of clinic time and uncertainty around issues such as funding for PGT and whose responsibility it comes under. Conclusions There is a need for training and education on reproductive options and referral for these options needs to be integrated within the health system. Developing more resources for both clinicians and patients is required as MND clinicians reported a lack of resources.

Reproductive Injustice and Genetic Counseling in the Socialist Politics of Disability

ABSTRACT This article examines how socialist experts were integrated into the entrenched global agenda of demographic security. The interplay of supranational and national priorities of reproductive politics is examined through three progressively developing practices: (1) research on “congenital malformations” as an argument for surveillance over women since the mid-1950s; (2) involvement of socialist experts in global debates regarding reproductive responsibility in the 1960s; and (3) revision of approaches to the “right to life” during the 1970s and 1980s. The layering and conversion of these practices explains the role of reproductive injustice in extensive segregation against people with disabilities in post-socialist countries.

Application of whole exome sequencing technology in the diagnosis of hereditary eye diseases

Objective: To evaluate the application of whole exome sequencing (WES) in the diagnosis of hereditary eye diseases. Methods: A total of 24 patients who came to the Obstetrics and Gynecology Hospital of Fudan University for reproductive genetic counseling from December 2020 to December 2023 with the main complaint of congenital eye disorders were included in this study. All cases had no known infections or exposure to known teratogenic drugs, karyotype and chromosome microarray analysis (CMA) abnormalities. Genomic DNA was extracted from the peripheral blood of the probands and their family members and tested for WES. Among them, three individual WES and 21 Trio WES were performed. Potential pathogenic sites were screened and analyzed by Sanger sequencing. For RPGRIP1:c.1611+26G>A site, minigene vector was constructed and RT-qPCR was performed to detect the effect of mRNA splicing. Results: A total of 24 families were collected in this study, of which 20 yielded positive results, achieving a diagnosis rate of 83.3% (20/24). The results involved 21 genes and identified 30 distinct variants, 19 of which were new variants reported. Prenatal diagnostic analysis of family 3 revealed that the fetus carried a c.6970G>T heterozygous nonsense mutation in the PRPF8 gene. The results of RT-PCR with the minigene vector at the non-classical splice site in family 24 indicated that the transcription product of the mutant plasmid was partially retained 104 bp in intron 12, resulting in a p.Glu538Valfs*12 alteration of the protein. Conclusions: The high detection rate of WES in the diagnosis of hereditary eye diseases further supports the advantages of its application as an important molecular detection tool for determining the etiology of hereditary eye diseases.

Strategies to Create a More Gender Identity Inclusive Learning Environment in Preclinical and Clinical Medical Education.

Recognition of the spectrum of gender identities has been a recent phenomenon in the medical profession. Over the past 20 years, medical literature related to gender identity diversity has increased several-fold, yet it more commonly addresses clinical care rather than aspects related to medical education. Medical educators continue to struggle with appropriate language and inclusive approaches when discussing gender-based aspects of medical education. Reproductive health education, including obstetrics and gynecology clerkships, is particularly vulnerable to missteps and anachronisms regarding gender identity.This article aims to provide preclinical and clinical medical educators with strategies to identify and predict situations where missteps related to gender identity inclusivity may occur in their curriculum or learning environment, and to develop approaches to improve gender identity inclusivity within medical education. The authors explore 3 areas that commonly pose challenges for medical educators: inclusive language and terminology, anatomy education, and reproductive genetics and genetic counseling. They hope the tools and strategies provided here will be useful to reproductive health medical educators across specialties to enable the realization of a more inclusive learning environment in reproductive health.

Reproductive decision-making following the diagnosis of an inherited metabolic disorder via newborn screening in Japan: a qualitative study.

The aim of the study was to describe the factors influencing the reproductive decision-making of carrier parents after the diagnosis of an inherited metabolic disorder in newborn screening in Japan. We conducted a semi-structured interview with 12 parents and analyzed data based on content analysis methodology. We identified 11 factors, including personal evaluation of recurrence risk, understanding of hereditary phenomena, concerns and desires for future planned children, concerns for older siblings, perceptions of diseases, degree of acceptance and denial of diseases, the opinions of others on having another child, optimism/faith in positive outcomes, self-evaluation of parental capability, factors unrelated to the disease, and the "right" time to expand the family. Perceptions and acceptance of disease are both important factors in reproductive decision-making, though these factors fluctuate continuously during the childbearing period. Therefore, effective reproductive genetic counseling will be considerate of the parents' fluctuating perceptions on reproduction. To ensure that the decision-making process is for the benefit of the parents and future children, long-term involvement of health care professionals is needed to assess the client's acceptance of the disease and their understanding of genetic phenomena and recurrence rates.

Clinical utility of exome sequencing in a pediatric epilepsy cohort.

Exome sequencing (ES) has played an important role in the identification of causative variants for individuals with epilepsy and has proven to be a valuable diagnostic tool. Less is known about its clinical utility once a diagnosis is received. This study systematically reviewed the impact of ES results on clinical decision-making and patient care in a pediatric epilepsy cohort at a tertiary care medical center. Pediatric patients with unexplained epilepsy were referred by their neurologist, and informed consent was obtained through an institutional review board-approved research ES protocol. For patients who received a genetic diagnosis, a retrospective chart review was completed of the probands and their relatives' medical records prior to and after genetic diagnosis. The following outcomes were explored: provider management recommendations, changes in care actually implemented, and anticipatory guidance provided regarding the proband's condition. Fifty-three probands met the inclusion criteria. Genetic diagnosis led to at least one provider recommendation in 41.5% families (22/53). Recommendations were observed in the following categories: medication, screening for non-neurological comorbidities/referrals to specialists, referrals to clinical research/trials, and cascade testing. Anticipatory guidance including information about molecular diagnosis, prognosis, and relevant foundations/advocacy groups was also observed. Results demonstrate the clinical utility of ES for individuals with epilepsy across multiple aspects of patient care, including anti-seizure medication (ASM) selection; screening for non-neurological comorbidities and referrals to appropriate medical specialists; referral to reproductive genetic counseling; and access to research, information, and support resources. To our knowledge, this is the first study to evaluate the clinical utility of ES for a pediatric epilepsy cohort with broad epilepsy phenotypes. This work supports the implementation of ES as part of clinical care in this population.

The utility of limited Spanish proficiency in interpreted genetic counseling sessions.

Professional interpreters are an integral component of healthcare for Spanish-speaking individuals with limited English proficiency (LEP). Research has demonstrated that errors in interpretation are common and can contribute to poor outcomes for Spanish-speaking clients. Providers with some Spanish proficiency may be able to detect clinically significant interpretation errors, potentially limiting negative clinical outcomes and helping to reduce health disparities for clients with LEP. This study aimed to identify the level of Spanish proficiency necessary for genetic counselors to be able to detect a majority of clinically significant errors made by a professional interpreter during a reproductive genetic counseling session. Practicing genetic counselors and genetic counseling graduate students were surveyed regarding their Spanish language background, experience working with interpreters, and self-rated Spanish proficiency. Participants then watched short video clips from three simulated reproductive genetic counseling sessions conducted with a professional interpreter and were tasked with identifying clinically significant interpretation errors. Survey responses were analyzed from 118 participants who met eligibility criteria. Participants who reported "basic" and "fair" Spanish proficiency detected an average of 36.5% and 67% of clinically significant errors, respectively. Those reporting "good" proficiency or higher detected more than 80% of errors. Overall self-rated Spanish proficiency was positively correlated with years of Spanish language education and individual measures of speaking, listening, and reading proficiency, indicating that self-report may be a reasonable measure of proficiency when the goal is error detection in an interpreted session. Genetic counselors with even minimal Spanish proficiency can detect clinically significant interpretation errors, allowing for the correction of these errors during the session. Genetic counselors with "basic" and "fair" may consider genetic counseling-specific Spanish language classes to increase their proficiency to be able to detect a majority of interpretation errors and thereby improve the quality of care and reduce health disparities for Spanish-speaking clients.

Cytogenetic evaluation of primary amenorrhea: a study of 100 cases at tertiary centre

BackgroundAmenorrhea is the absence of menstruation in women of reproductive age. The physiology of menstruation and reproduction has a strong correlation with the expression of the X chromosome. Early referral for cytogenetic evaluation is recommended for the identification of underlying chromosomal aberrations in amenorrhoea patients. This study aims to estimate the frequency and types of chromosomal abnormalities in primary amenorrhoea (PA) patients in western India and correlate their hormonal profile and sonographic findings with chromosomal reports.Patients and methodsClinical features of 100 patients along with their hormonal profile and sonographic findings were recorded. Karyotyping was done after taking informed consent from the patients. Molecular cytogenetic technique was used to confirm marker chromosomes and ring chromosomes.ResultsThe results revealed 89% of PA with normal female karyotype (46,XX) and 11% with different abnormal karyotypes. Majority of females with normal karyotype were having Mullerian defects and among them most of them were categorized under Rokitansky syndrome. Among the abnormal karyotype constituents, 27.3% numerical abnormalities, all were Turner syndrome; pure and mosaic. Four cases (36.4%) showed male (XY) karyotype. The other four cases (36.4%) showed structural abnormalities, among which three cases showed X-associated structural abnormality and one case showed balanced translocation.ConclusionThis study emphasizes the need for cytogenetic analysis as an integral part of the diagnostic protocol in the case of PA for precise identification of chromosomal abnormalities; and for appropriate reproductive management. Early detection of abnormalities is necessary for guidance to reproductive options and genetic counselling.

Prenatal diagnosis study using array comparative genomic hybridization for genotype-phenotype correlation in 772 fetuses

ObjectiveThe aim was to evaluate the main indications for prenatal diagnosis, the prevalence of abnormal copy number variations (CNVs), correlate them with clinical findings, analyze the prevalence of VUS, report the rare variants found and additionally highlight the clinical importance of microarray-based comparative genomic hybridization (aCGH) in prenatal diagnosis. Study designWe retrospectively analyzed a cohort of 772 fetuses with indication for genetic study in two tertiary hospitals, in a 9-years-period, using aCGH. ResultsOur results demonstrated 8.3 % (6.4–10.5 %, 95 % CI) detection rate of pathogenic CNVs. Within this group, the main indication was structural malformations (57 %) mainly involving central nervous system, skeletal and cardiac systems. Pathogenic results in cases with multiple malformations were higher than in cases with isolated anatomical system malformations showing statistical significant differences (p < 0.001). The second indication where we found more pathogenic CNVs was increased nuchal translucency (5–6.4 mm). In fact, the rate of pathogenic CNVs did not show significant differences between structural and non-structural malformations (p > 0.001), highlighting the relevance of genetic study by aCGH also in cases with no structural malformations.A total of 217 fetuses with CNVs classified as VUS were identified, mainly involving chromosomes X, 1 and 16. ConclusionOur findings demonstrate 4.9 % (4.2–5.6 %, 95 % CI) increased in the diagnostic yield using aCGH compared to the use of conventional karyotype alone, confirming that the aCGH can improve the accuracy of prenatal diagnosis. Our survey provides a full genotype-phenotype analysis that can be clinically useful for the classification of variants in the context of prenatal setting, helping to provide a better reproductive genetic counselling.

Identification of a familial complex chromosomal rearrangement by optical genome mapping

BackgroundComplex chromosomal rearrangements (CCRs) are rare chromosomal structural variations, containing a variety of rearrangements such as translocation, inversion and/or insertion. With the development of cytogenetic and molecular genetic techniques, some chromosomal rearrangements that were initially considered to be simple reciprocal translocations in the past might eventually involve more complex chromosomal rearrangements.Case presentationIn this case, a pregnant woman, who had a spontaneous abortion last year, had abnormal prenatal test results again in the second pregnancy. Applying a combination of genetic methods including karyotype analysis, chromosomal microarray analysis, fluorescence in situ hybridization and optical genome mapping confirmed that the pregnant woman was a carrier of a CCR involving three chromosomes and four breakpoints, and the CCR was paternal-origin. Her first and second pregnancy abnormalities were caused by chromosomal microdeletions and microduplications due to the malsegregations of the derivative chromosomes.ConclusionsWe presented a rare familial CCR involving three chromosomes and four breakpoints. This study provided precise and detailed information for the subsequent reproductive decision-making and genetic counselling of the patient.

Gonadal mosaicism in GNAO1 causing neurodevelopmental disorder with involuntary movements; two additional variants

BackgroundGNAO1 encodes an alpha subunit of the heterotrimeric guanine nucleotide-binding proteins (G proteins). Mutations in GNAO1 result in two clinical phenotypes: Early infantile epileptic encephalopathy 17 (EEIE17-OMIM #615473) and Neurodevelopmental disorder with involuntary movements (NEDIM-OMIM #617493). Both are inherited as autosomal dominant disorders and originate mainly as de novo. Only a few are reported as gonadal mosaicism. Materials and methodsWe recruited and retrospectively reviewed five patients from two families seen at King Faisal Specialist Hospital and Research Centre in Riyadh (KFSHRC). ResultsAll patients presented with severe neurodevelopmental disorder, followed by progressive dystonia and hyperkinetic movements. In addition, none of the patients had seizures which was consistent with NEDIM phenotype. The specific diagnosis was not clinically entertained and was only found on whole exome sequencing (WES), which identified two variants (c.724-8G > A & c.709G > A). Both variants were previously reported as pathogenic de novo in patients with NEDIM, and one was reported as parental gonadal mosaicism. ConclusionWe report these variants as additional variants in GNAO1 gene that may be inherited as parental gonadal mosaicism. Both variants resulted in NEDIM with no observed clinical differences in the severity than the reported cases. This noticeable reported association between GNAO1 gene associated disorders and gonadal mosaicism should be considered in reproductive genetic counselling of affected families. Furthermore, in view of these reports, more studies with prospective data collection to explore the association between GNAO1 and gonadal mosaicism and the underlying mechanisms will be necessary.

Molecular Epidemiology and Hematologic Characterization of Thalassemia in Guangdong Province, Southern China.

Introduction: About 2% of the population in the world are carriers of the thalassemia gene. Thalassemia is highly prevalent in Southern China, and traditional clinical testing methods would cause missed diagnosis of partial static thalassemia. Here, we reviewed and summarized a set of simple and clinically feasible thalassemia detection protocols adopted by the Prenatal Diagnosis and Reproductive Center of our hospital. Methods: From January 1, 2015, to December 31, 2020, 31 512 peripheral blood samples and 3828 prenatal samples were collected in our study. All the peripheral blood samples were performed through thalassemia screening by routine blood tests and hemoglobin electrophoresis and gene detection. The prenatal diagnosis would be implemented for the fetus if the parents were carriers of the same type of thalassemia. Results: A total of 6137 (19.48%) cases were diagnosed as thalassemia, in which 4749 (15.07%) were α-thalassemia, 1196 (3.80%) were β-thalassemia and 192 (0.61%) were co-inheritance of α- and β-thalassemia. For prenatal samples, 3160 (82.55%) cases were diagnosed as thalassemia, in which 2021 (52.80%) were α-thalassemia, 997 (26.05%) were β-thalassemia and 142 (3.71%) were co-inheritance of α- and β-thalassemia. In addition, we also found five novel mutations, including NC_000016.9:g.223681-227492del3812; HBA1: c.301-31_301-24delCTCGGCCCinsG; HBA2: c.95+7C>T for α-thalassemia and HBB: c.263_276delCACTGAGTGAGCTG; HBB: c.315+143G>A for β-thalassemia. Conclusion: The present study updates the epidemiological characteristics and mutation spectrum of thalassemia in Southern China and demonstrated five novel mutations. Our research provides a reference for clinical diagnosis and treatment, prenatal diagnosis, or reproductive genetic counseling for patients with thalassemia in Guangdong.

Elucidating clinical phenotypic variability associated with the polyT tract and TG repeats in CFTR.

Biallelic pathogenic variants in CFTR manifest as cystic fibrosis (CF) or other CFTR‐related disorders (CFTR‐RDs). The 5T allele, causing alternative splicing and reduced protein activity, is modulated by the adjacent TG repeat element, though previous data have been limited to small, selective cohorts. Here, the risk and spectrum of phenotypes associated with the CFTR TG‐T5 haplotype variants (TG11T5, TG12T5, and TG13T5) in the absence of the p.Arg117His variant are evaluated. Individuals who received physician‐ordered next‐generation sequencing of CFTR were included. TG[11‐13]T5 variant frequencies (biallelic or with another CF‐causing variant [CFvar]) were calculated. Clinical information reported by the ordering provider or the individual was examined. Among 548,300 individuals, the T5 minor allele frequency (MAF) was 4.2% (TG repeat distribution: TG11 = 68.1%, TG12 = 29.5%, TG13 = 2.4%). When present with a CFvar, each TG[11‐13]T5 variant was significantly enriched in individuals with a high suspicion of CF or CFTR‐RD (personal/family history of CF/CFTR‐RD) compared to those with a low suspicion for CF or CFTR‐RD (hereditary cancer screening, CFTR not requisitioned). Compared to CFvar/CFvar individuals, those with TG[11‐13]T5/CFvar generally had single‐organ involvement, milder symptoms, variable expressivity, and reduced penetrance. These data improve our understanding of disease risks associated with TG[11‐13]T5 variants and have important implications for reproductive genetic counseling.

The COVID-19 pandemic and reproductive genetic counseling: Changes in access and service delivery at an academic medical center in the United States.

The COVID‐19 pandemic widely disrupted the delivery of healthcare services, including genetic counseling. To ensure continuity of care, the reproductive genetic counselors at a large academic medical center in the United States rapidly transitioned their practice from 90% in‐person patient consultations to a predominantly telehealth model. The present study describes this transition in regard to patient access to genetic counseling and genetic screening. A chart review of patients seen by the reproductive genetic counselors from January 2020 to August 2020 was completed. The time frame included the three months prior to the COVID‐19 pandemic and the first five months during COVID‐19. Patient demographics and clinical and appointment data were compared between the pre‐COVID‐19 and during‐COVID‐19 timeframes. Overall, 88.6% of patients were seen via telehealth during COVID‐19 and there was no significant difference based upon patient age (p = .20), indication for appointment (p = .06), or gestational age (p = .06). However, non‐English speaking patients were more often seen in‐person than by telehealth (p < .001), and more patients residing farther from the clinic were seen via telehealth (p = .004). During‐COVID‐19 results for prenatal cell‐free DNA screening and expanded carrier screening were delayed (p < .001). Additionally, after consenting to screening, patients seen during COVID‐19 were more likely to not complete a sample collection for their intended screening when compared to those seen pre‐COVID‐19 (OR = 6.15, 95% CI = 1.43–26.70, p = .015). Overall, this study supports that access to genetic counseling services and genetic screening can be maintained during a global pandemic like COVID‐19. Genetic counselors are well‐equipped to pivot swiftly during challenging times; however, they must continue to work to address other barriers to accessing genetic services, especially for non‐English speaking populations. Future studies are needed to pose solutions to the obstacles confronted in this service delivery model during a global pandemic.

Trends in coverage and reimbursement for reproductive genetic counseling in New Jersey by multiple payers from 2010 to 2018

Lack of consistent insurance coverage for genetic counseling services billed under Current Procedural Terminology (CPT) code 96040 creates a barrier for access to this service. This retrospective study examined coverage and reimbursement for reproductive genetic counseling encounters billed under CPT code 96040 as a professional fee over an eight-year period at Rutgers Robert Wood Johnson Medical School, a regional perinatal center in New Jersey, a state requiring licensure. Descriptive statistics were tabulated to assess the disparity between Medicare/Medicaid, Managed Care Medicaid, and commercial insurance payers, including how often encounters were covered and if reimbursed, at what percentage of the amount billed. A comparison of individual plan types (Health Maintenance Organization, Point of Service, and Preferred Provider Organization) was carried out. Overall trends in reimbursement were assessed across payers. The study found 61% of 60-min encounters billed to Medicare/Medicaid, Managed Care Medicaid, and commercial insurance payers received coverage. Of all covered 60-min encounters billed to Managed Care Medicaid and commercial insurance payers, an average of 36% of the amount billed was reimbursed. Medicare/Medicaid encounters were never reimbursed. Commercial insurance covered 65% of encounters billed but this varied between payers. Across all payers, an overall downward trend of reimbursement was demonstrated over the eight-year period. Lack of consistent service coverage creates a barrier and patients cannot universally access genetic counseling services. Steps to improve coverage need to include passing of legislation, notably the next bill to replace the former H.R. 3235, 'Access to Genetic Counselor Services Act of 2019' and provisions within third-party payers that allow for credentialing of genetic counseling providers.

Genetic counselors' experiences with transgender individuals in prenatal and preconception settings.

Many transgender individuals want to have children and are pursuing reproductive care. Limited research has described the experiences of transgender individuals during pregnancy, and no known studies have examined reproductive genetic counseling sessions with this patient population. To understand what topics and considerations are explored within this sector of reproductive care, prenatal and preconception genetic counselors that have seen a transgender patient and/or transgender partner of a patient were recruited through an email blast to members of the National Society of Genetic Counselors. Nine genetic counselors completed phone interviews. Content analysis was used to identify, quantify, and examine the concepts within the transcripts. Six major themes emerged: (1) Trans individuals were referred for common genetic counseling indications, (2) genetic counselors were driven to think of more inclusive language, (3) genetic counselors considered ways to make written materials more inclusive, (4) trans individuals expressed discomforts in the prenatal/preconception setting, (5) genetic counselors observed challenges with the care team, and (6) genetic counselors felt underprepared. This study identifies areas within reproductive spaces of genetic counseling that could be more inclusive, particularly relating to commonly used gendered language and written materials, and provides training recommendations for genetic counselors. Additionally, we outline the reported areas of discrimination for these patients and partners, and discuss ways that genetic counselors can be advocates for respectful and equitable care within their clinics.

INCREASING SCALE AND THROUGHPUT OF TELEHEALTH GENETIC COUNSELING ACROSS THE SPECTRUM OF REPRODUCTIVE CARE, WHILE MAINTAINING HIGH PATIENT SATISFACTION

Multiple professional societies recommend genetic counseling alongside reproductive genetic testing, including the American Society for Reproductive Medicine and the American College of Obstetrics and Gynecology. However, access to genetic counselors (GCs) continues to be an issue. Efforts are being made to remedy this with increased GC throughput and novel approaches to service delivery. We sought to describe one such approach by examining the volume, scope, and capacity of a high throughput telehealth genetic counseling service that provides care to reproductive patients across the country. Retrospective review of consult data from a telehealth genetic counseling service. We examined data for reproductive genetic counseling consults that occurred between 1/1/2018 and 12/31/2019. Extracted data included indication, time required to complete consult, and patient satisfaction. To assess throughput, the number of reproductive consults a GC could complete per week was estimated. In 2018, 541 reproductive genetic counseling consults were performed, and 1922 were performed in 2019. Care was provided to patients from reproductive endocrinology clinics, genetic testing laboratories, and maternal fetal medicine clinics. Indications included carrier screening, preimplantation genetic testing (PGT), egg donor screening, abnormal aneuploidy screen, advanced maternal age, ultrasound findings, and family history of a genetic condition. The mean time to complete all aspects of a consult (preparation, counseling, and writing genetic counseling summary report) was 40.6 minutes (standard deviation 6.7 minutes). At 40.6 minutes per consult, a full-time GC working in this efficient and high-throughput model can perform 53 consults per week, assuming the same mix of routine and complex cases. This is more than double the weekly caseloads for reproductive GCs reported by the National Society of Genetic Counselors (15.6-20.5 consults per week), which primarily represents traditional lower throughput models. Despite the high throughput nature of the service, patient satisfaction remained high during the study period (95.6%). Consistent with their complexity, PGT consults took longer than other consults in preparation and counseling (preparation: 13.0 minutes vs. 4.0 minutes, p<0.001; counseling: 29.2 minutes vs. 16.0 minutes, p<0.001; documentation: 10.4 minutes vs. 9.0 minutes, p=0.18). In contrast, carrier screening consults took less time than other consults (preparation: 5.5 minutes vs. 9.6 minutes, p<0.001; counseling: 18.3 minutes vs. 21.2 minutes, p<0.001; documentation: 7.5 minutes vs. 11.4 minutes, p<0.001). Genetic counseling provided by a national telehealth organization covers the full range of reproductive indications, from routine to complex. The approach is scalable, with a 3.5 fold increase in consult volumes from 2018 to 2019. Given the high patient satisfaction, increased throughput, and nation-wide nature of this approach, it is a promising option for increasing access to reproductive genetic counseling.

Mutations of the cystic fibrosis transmembrane conductance regulator gene in males with congenital bilateral absence of the vas deferens: Reproductive implications and genetic counseling (Review).

Congenital bilateral absence of the vas deferens (CBAVD) is predominantly caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CBAVD accounts for 2–6% of male infertility cases and up to 25% of cases of obstructive azoospermia. With the use of pre-implantation genetic diagnosis, testicular or epididymal sperm aspiration, intracytoplasmic sperm injection and in vitro fertilization, patients affected by CBAVD are able to have children who do not carry CFTR gene mutations, thereby preventing disease. Therefore, genetic counseling should be provided to couples receiving assisted reproductive techniques to discuss the impact of CFTR gene mutations on reproductive health. In the present article, the current literature concerning the CFTR gene and its association with CBAVD is reviewed.

Novel compound heterozygous DNAAF2 mutations cause primary ciliary dyskinesia in a Han Chinese family.

Primary ciliary dyskinesia (PCD), which commonly causes male infertility, is an inherited autosomal recessive disorder. This study aimed to investigate the clinical manifestations and screen mutations associated with the dynein axonemal assembly factor 2 (DNAAF2) gene in a Han Chinese family with PCD. A three-generation family with PCD was recruited in this study. Eight family members underwent comprehensive medical examinations. Genomic DNA was extracted from the participants' peripheral blood, and targeted next-generation sequencing technology was used to perform the mutation screening. The DNAAF2 expression was analyzed by immunostaining and Western blot. The proband exhibited the typical clinical features of PCD. Spermatozoa from the proband showed complete immotility but relatively high viability. Two novel compound heterozygous mutations in the DNAAF2 gene, c.C156A [p.Y52X] and c.C26A [p.S9X], were identified. Both nonsense mutations were detected in the proband, whereas the other unaffected family members carried either none or only one of the two mutations. The two nonsense heterozygous mutations were not detected in the 600 ethnically matched normal controls or in the Genome Aggregation Database. The defect of the DNAAF2 and the outer dynein arms and inner dynein arms were notably observed in the spermatozoa from the proband by immunostaining. This study identified two novel compound heterozygous mutations of DNAAF2 leading to male infertility as a result of PCD in a Han Chinese family. The findings may enhance the understanding of the pathogenesis of PCD and improve reproductive genetic counseling in China.

Regional Differences in the Beliefs and Practices Among Adults with Sickle Cell Disease Regarding Reproductive Health and Family Planning: A Sub-Analysis

Background. Sickle cell disease (SCD) remains the most common genetic hematologic disorder, with a disproportionally high incidence and prevalence in African countries. It is associated with an increased risk of maternal and infant morbidity and mortality compared to the general population. As more young adults living with SCD reach healthier reproductive ages, it is imperative that there is open communication between providers and patients regarding reproductive health, maternal risks associated with childbirth, and the risk of having children who inherit SCD. It is also important that providers understand reproductive health knowledge and perceptions within this population and methods to improve family planning education. We performed a survey-based study aimed to quantify current knowledge and perceptions regarding reproductive health choices, family planning and genetic counseling-presented in another abstract-. Here we present a sub-analysis, aiming to quantify differences, based on the participants region, concerning reproductive health knowledge and perceptions amongst adults with SCD. Methodology. All study participants were at least 18 years old and have a SCD diagnosis. They were asked to complete an anonymous survey instrument consisting of 43 questions, administered using Qualtrics Survey Software. The survey was comprised of questions about participants' demographics, knowledge base and perceptions about reproductive health and genetic counseling. Participants were recruited using convenience sampling in two ways. The first was through reaching sickle cell patient groups online via social media through Facebook and Twitter. The second was at an adult SCD clinic where participants were invited to complete the survey in clinic or afterwards. 152 participants accessed the survey, and 105 that completed more than 90% of the survey were included in the primary analysis. Further analysis was done to compare data from 70 participants who did not migrate from their reported birth country. Comparison groups were generated using reported birth country and current location. Forty-seven participants from North American (U.S. and Canada) and 23 from African Countries (Nigeria, Zambia, Kenya, and South Africa) were included in this analysis. Results. Demographics: Among the 70 analyzed, 47 (67.1%) respondents were from North America (N.A.) and 23 (32.9%) were from African Countries (A.C). Knowledge: People from both N.A. and A.C. agreed that women with SCD were at higher risk of pregnancy complications (91.5% and 87%, respectively), and understood the chance of having a child with SCD if both parents have the trait (78.7% and 78.3%). Perception: Participants from N.A. reported receiving most of their information about family planning, partner screening, and reproductive health from healthcare providers more frequently than participants from A.C. (67% vs 39%). More participants from A.C, 21 (91.3%), agreed that having children in the future was important to them, while 21 (45%) of the participants from N.A agreed to this. Participants from A.C. and N.A. equally agreed that is it important to know if their partner has the sickle cell trait (SCT) (95.7% and 93.6%). However, more participants from A.C., 21 (91.3%), reported having any discussion with their partner about being screened for the SCT, versus 29 (61.8%) from N.A. Participants from N.A. and A.C. were equally knowledgeable about what a genetic counselor is (72% v. 70%, respectively), and utilized genetic counseling at low rates (37% v. 39.1%, respectively). Most participants reported that they do not know how to get in contact with a genetic counselor in their community, 31 (66%) from N.A. and 18 (78.3%) from A.C. Many have not been referred to a genetic counselor in the past by a healthcare provider, 39 (83%) from N.A. and 20 (87%) from A.C. Conclusion. Our study suggests that there are differences in reproductive health and genetic counseling knowledge and perceptions when comparing SCD participants living in two world regions. Independently of regional differences, many people with SCD appear to lack key reproductive health and genetic counseling knowledge and resources. We believe there is a need for improved communication between providers and patients in family planning education, as well as further studies to address access to reproductive health and genetic counseling resources. Disclosures Nunez: American Board of Genetic Counseling: Membership on an entity's Board of Directors or advisory committees; Foundation for Women and Girls with Blood Disorders: Membership on an entity's Board of Directors or advisory committees. De Castro:Novartis: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy.