Genetic Carrier Screening Research Articles

Management of Prenatal Expanded Genetic Carrier Screening Results for Autosomal Recessive Sensorineural Hearing Loss.

Expanded carrier screening (ECS) identified couples at-risk to have a baby with an autosomal recessive genetic condition. Several genes implicated in sensorineural hearing loss (SNHL) are included in prenatal or preconception genetics ECS testing. Early identification of SNHL risk may enable prognostication of hearing loss, early educational intervention, and minimization of unnecessary diagnostic testing. We sought to describe cases where ECS enabled early SNHL-risk identification. Retrospective chart review. Maternal-Fetal Care Center and Otolaryngology department at an academic tertiary hospital. Medical records of parent-infant dyads with positive ECS results for variants in autosomal recessive SNHL genes were reviewed. Data regarding genetic diagnostic testing, newborn hearing screening, time to HL diagnosis, audiological evaluation, and clinical consultations were compiled. Fifteen pregnant with positive ECS results for SNHL were referred for consultation with a pediatric otolaryngologist and genetic counselor. Generally, these couples were highly educated and adequately insured. 14 had pathogenic variants for GJB2 and 1 for USH2A. Four couples pursued prenatal genetic diagnosis via amniocentesis; 11 couples deferred genetic testing to the postnatal period or waited for initial hearing evaluation. Six babies inherited biallelic GJB2 mutations. Four were found to have SNHL on ABR by age 5 weeks and received follow-up management, 1 had a normal hearing evaluation despite being gene-positive, and 1 was lost to follow-up before hearing evaluation. Carrier screening and confirmatory prenatal or neonatal genetic testing provided considerable lead time for early audiometric testing and appropriate intervention services including hearing aid fitting.

Implementation of Genetic Carrier Screening at Gynecologic-Related Visits

ObjectiveTo increase patients’ knowledge and access to genetic carrier screening (GCS) in a gynecologic setting by implementing a protocol to universally offer GCS education and screening to reproductive-age women during the preconception period at gynecologic-related visits. DesignThe model for improvement quality improvement process model was used to guide this initiative. Local Problem/SettingScreening for genetic disease has been a part of preconception and genetic care for the past 50 years. Despite its longstanding presence and better accessibility and affordability of testing, there are no established protocols to universally offer screening to reproductive-age women during preconception care in the United States. The project was implemented at an outpatient gynecology clinic in Phoenix, Arizona. ParticipantsFifty-one women ages 18 to 51 years. Intervention/MeasurementsA protocol was implemented to universally offer expanded GCS and health education to reproductive-age women during the preconception period at gynecologic-related visits. Women’s responses to being offered GCS and the rationale for their response was documented on a spreadsheet. ResultsAll 51 participants were offered GCS during their visit. None of those 51 participants had any previous knowledge of GCS. All 51 participants declined GCS; reasons included the following: would consider it once closer to childbearing (53%), did not have any childbearing plans (31.3%), did not have any further childbearing plans (9.8%), or were not worried about the possibility of genetic disease (5.8%). None cited cost as a reason for declining GCS. After project completion, 3 of the 51 participants returned to the clinic to undergo GCS, and the clinic has adopted the intervention described here as its standard of care for patients who meet criteria for GCS. ConclusionIt is imperative to provide health education about GCS to women during preconception care so that they can make informed choices about family planning.

Significance of Variants of Uncertain Significance: The Human Cost of Genetic Uncertainty.

This piece narrates the journey of Maria (name of the mother has been altered to protect the family's privacy), a new mother confronting her newborn's unexpected diagnosis of very long chain acyl-CoA dehydrogenase (VLCAD) deficiency, despite undergoing proactive genetic carrier screening within a consanguineous marriage. It highlights the emotional and systemic challenges arising from the lack of diversity in genetic databases, which, in this case, failed to detect pathogenic variants in Maria and her husband. Maria's story sheds light on situations where a masked variant of uncertain significance (VUS) necessitates consultation with a trained genetics specialist and underscores the urgent need for a more equitable healthcare system.

Mutation Analysis of Exon 1 in the Hemoglobin Subunit Beta (HBB) Gene in Beta-Thalassemia.

Introduction Thalassemia is a widely prevalent monogenic hematological disorder found worldwide. It exists in two forms: alpha- and beta-thalassemia. Alterations in the hemoglobin subunit beta (HBB) gene cause beta-thalassemia, with missense and point mutations affecting beta-globin synthesis. Consequently, genetic screening for beta-thalassemia is essential for genetic counseling, carrier screening, and prenatal diagnosis. Aim and objective This study aims to examine and identify mutations in the exon 1 region of the HBB gene in beta-thalassemia patients from the Vijayapura region. Methods This study involved 47 clinically diagnosed children with beta-thalassemia from a hospital in Vijayapura, India. Detailed clinical histories of all patients were recorded. Genomic DNA was extracted from the blood samples of these patients and subjected to polymerase chain reaction (PCR) using exon-specific primers for the HBB gene. The PCR products were then sequenced using the capillary-based Sanger sequencing method to identify mutations in the HBB gene. Results A total of 47 clinically diagnosed beta-thalassemia patients were included in the study, comprising 30 males and 17 females, aged between one and 20 years. Sequencing analysis of exon 1 in the beta-globin gene identified 17 beta-thalassemia variants. The most common mutation observed was T>G, G>C, C>A, and C>T in the exon 1 region of the HBB gene. Conclusion This study identifies the pattern of beta-thalassemia mutations, aiding in the prevention of the disorder through prenatal diagnosis and genetic counseling. Mutations can alter codon sequences, affecting protein production. Research highlights the importance of a primary prevention program to analyze mutations and sequence variations at the molecular level, thereby helping to address numerous genetic disorders.

Expanded targeted preconception screening panel in Israel: findings and insights

BackgroundWe aimed to analyse the efficacy and added value of a targeted Israeli expanded carrier screening panel (IL-ECSP), beyond the first-tier test covered by the Israeli Ministry of Health (IMOH)...

The Uptake of Partner Participation in Sequential Preconception Carrier Screening

Introduction: Carrier screening that is performed in the preconception period allows for couples at risk for having children affected with certain single gene (Mendelian) conditions to be identified. This is the most optimal timeframe to perform such screening. Most obstetric providers utilize a sequential process in which the patient first undergoes screening and their partner is only offered testing if the initial results reveal that the first is a carrier for one or more autosomal recessive (AR) deleterious variants. If the partner fails to undergo screening, the couple cannot obtain meaningful and actionable risk information for future or current pregnancies. In this study, we sought to assess the frequency of completed carrier screening risk assessment among individuals and couples who were undergoing preconception screening at two prenatal screening programs staffed by genetic counselors and geneticists. Materials and Methods: We reviewed the screening outcomes for individuals and couples who presented for preconception carrier screening from January 1, 2020 through December 30, 2021 at Insight Medical Genetics and the clinical genetics program at Northwestern Medicine. All individuals received pretest genetic counseling prior to screening and posttest counseling after results were available. We evaluated individuals who were found to be a carrier of at least one deleterious variant and whether the partner of that person underwent carrier screening, and, if so, which type of screening. Results: 548 patients who identified as women underwent preconception carrier screening during the study period, along with 3 men presenting for initial screening. These screens consisted of a panel containing primarily autosomal recessive conditions with a few X-linked conditions. 247 individuals (45.1%) were positive for at least one pathogenic variant; of these, 244 (98.8%) were variants in genes associated with autosomal recessive conditions. A total of 219 partners (88.7%) underwent carrier screening, including the 3 female partners of the men who initiated carrier screening. Of note, 4 of the patients who underwent carrier screening reported not having a partner at the time of screening; accordingly, the partners who underwent screening represent 89.8% of individuals eligible for partner screening following an initial positive result. Of the 219 partners who underwent carrier screening, 201 (91.8%) chose a carrier screening panel of 150+ conditions, while 18 chose a more limited panel that included the gene(s) of relevance based on their partner’s results, with or without additional genes relevant to their learned/self-identified ethnicity or race. Conclusions: Approximately 10% of couples presenting for preconception genetic counseling and carrier screening found to be at potential risk for a child with an autosomal recessive condition did not obtain the requisite information to fully assess their risk of having an affected child. It is possible that the frequency of couples who do not obtain complete and actionable screening information is even higher when carrier screening is provided without the assistance of certified genetic counselors or geneticists. Recently, cell free DNA-based maternal screening has been introduced that assesses the risk for a limited number of genetic conditions in the fetus that may not require assessment of the partner. Nonetheless, providers must communicate to their patients that meaningful risk information can only be obtained when the partner undergoes screening in cases where the initial member of the couple is found to be a carrier of at least one autosomal recessive condition. Laboratories and professional societies need to develop effective educational outreach to patients and providers alike to improve the screening process for couples who want to determine if they are at risk to have a child with an inherited condition.

Reproductive genetic carrier screening in pregnancy: improving health outcomes and expanding access.

Reproductive genetic carrier screening (RGCS) serves to screen couples for their risk of having children affected by monogenic conditions. The included conditions are mostly autosomal recessive or X-linked with infantile orearly-childhood onset. Cystic fibrosis, spinal muscular atrophy, and hemoglobinopathies are now recommended by the American College of Obstetricians and Gynecologists (ACOG) for universal screening. Recommendations for further RGCS remain ethnicity based. The American College of Medical Genetics and Genomics and the National Society of Genetic Counselors in recent years have recommended universal expanded-panel RGCS and moving towards a more equitable approach. ACOG guidelines state that offering RGCS is an acceptable option, however it has not provided clear guidance on standard of care. Positive results on RGCS can significantly impact reproductive plans for couples, including pursuing invitro fertilization with preimplantation genetic testing, prenatal genetic testing, specific fetal orneonatal treatment, or adoption. RGCS is a superior approach compared to ethnicity-based carrier screening and moves away from single race-based medical practice. We urge the obstetrics and gynecology societies to adopt the guidelines for RGCS put forward by multiple societies and help reduce systemic inequalities in medicine in our new genetic age. Having national societies such as ACOG and theSociety for Maternal-Fetal Medicine officially recommend and endorse RGCS would bolster insurance coverage and financial support by employers for RGCS. The future of comprehensive reproductive care in the age of genomic medicine entails expanding access so patients and families can make the reproductive options that best fit their needs.

Beyond severity: utility as a criterion for setting the scope of RGCS.

Reproductive genetic carrier screening (RGCS) allows prospective parents to identify and act upon their chances of having a child with a genetic condition. In deciding which genetic conditions to include in RGCS, severity is often used as a criterion. However, the concept is inherently complex, subjective and multidimensional, and determinations of severity will remain intractably contested. We propose the concept of utility as a criterion for setting the scope of RGCS, and put forward two central arguments for doing so. First, utility is a more appropriate and effective concept as it responds to context and makes an explicit connection between the purpose of RGCS and the value of information obtained for that purpose: namely, to facilitate reproductive decision-making. Utility comprises both clinical and personal utility, and varies according to the availability and accessibility of reproductive options, including pre-implantation genetic testing, prenatal genetic diagnosis, and termination of pregnancy. Second, there are ethical reasons for preferring utility over severity. Utility is a property of the information gleaned from RGCS, while severity is a property of a genetic condition or of an instance of this condition in a person. While consideration of the severity of genetic conditions is not lost when focusing on utility, the need to rely on value judgements regarding the quality of life of people who live with genetic conditions is circumvented. Therefore, utility should replace severity as justification for the inclusion of genetic conditions in RGCS programmes.

Screening of voluntary blood donors for beta-thalassemia trait in an endemic area in Northwest India for 15 years: Results and future directions after screening more than 300 thousand donors

Abstract: BACKGROUND: North-West India has a high prevalence of the Thalassemia, and the Beta Thalassemia Trait often remains undetected in the population. Recognizing the need to address this public health issue, we initiated “Blood the Lifeline” project in 2006 with the aim to eradicate Thalassemia through proactive measures, including screening of voluntary blood donors. AIM: The primary aim of this study was to screen voluntary blood donors in an endemic area in northwestern India for Thalassemia trait. The study aimed to determine its prevalence, identify gender and ethnic group-wise distributions, and assess the implications for future interventions. METHODS: The screening program was conducted from January 2006 till December 2022. Voluntary blood donors were recruited from the target area and underwent Thalassemia trait screening. The screening process involved High Performance Liquid Chromatography using VARIANT II fully automated HPLC system to identify Thalassemia trait. Data regarding the total number of cases screened, gender distribution, ethnic group-wise distribution, and positive and negative cases were collected and analyzed. Screening Process: EDTA Pilot tube from each donor was collected and analyzed within 24 hrs of collection. RBC Counts, Hb Concentration, MCV, MCH, RDW-SD were noted to differentiate between Iron Deficiency Anaemia & thalassemia trait & following Criteria’s were taken into account: Total RBC Count: > 5.0 x 106 / micro-liter, Hb: < 11.7 g/dl, MCV: < 77 fl, MCH: < 28 pg & RDW-SD: < 45 fl. A combination of Formulas like Mentzer’s index= MCV/RBC <13; Shine and Lal Index (S&L) = MCV × (MCH/100) < 1530; Green & King (MCV2) × RDW]/ (Hb × 100) < 65 were used for screening. All the above formulas were introduced into the Blood Bank Software to exclude out the blood units requiring screening & confirmation. If any of the samples were positive on initial screening, then confirmatory test was done by demonstrating the elevation of concentration of HbA2 by HPLC VARIANT II fully automated analyser. RESULTS: A total of 377,503 voluntary blood donors for a 16 year period were screened and data was analysed .The Mean Hemoglobin of positive donors was 12.1 gm/dl; Mean RBC Count was 6.24 m/cu mm, MCV 67.79 fl, MCH 21.04 pg, RDW-SD 42.11fl & HbA2 was 7.48%. The majority of positive cases were found in the Sindhi (16.68%), Punjabi (10.32%), and Muslim (9.81%) ethnic groups. The Rajasthani population accounted for 6.01% of positive cases. CONCLUSION: This comprehensive screening program revealed a relatively high prevalence of Thalassemia trait in 2.29% of the screened population. The communities with higher prevalence (Sindhi, Punjabi, and Muslim) were educated about the disease and a targeted screening program will be further carried out in these ethnic groups. The data helped in planning genetic counseling, carrier screening, and pre-marital screening programs to reduce the transmission of Thalassemia in these populations. By focusing efforts on specific groups and locations with higher prevalence, a community based approach to prevent the birth of children with Thalassemia major is being implemented. It is also being used for analyzing the implications of different local policies pertaining to Thalassemia trait in the region. Collaborative efforts between healthcare organizations, community leaders, and governmental agencies are crucial to address the burden of Thalassemia and work towards its eradication. The results of this study serve as a foundation for future initiatives aimed at minimizing the impact of Thalassemia at a community level.

Medicare-funded reproductive genetic carrier screening in Australia has arrived: are we ready?

Medicare-funded reproductive genetic carrier screening in Australia has arrived: are we ready?

High carrier frequency of CYP21A2 gene mutations in Southern India - underscoring the need for genetic testing in Congenital Adrenal Hyperplasia.

Congenital Adrenal Hyperplasia (CAH) is one of the highly prevalent autosomal recessive endocrine disorders. The majority of CAH cases result from mutations in the CYP21A2 gene, leading to 21-hydroxylase deficiency. However, with the pseudogene-associated challenges in CYP21A2 gene analysis, routine genetic diagnostics and carrier screening in CAH are not a part of the first-tier investigations in a clinical setting. Furthermore, there is a lack of data on the carrier frequency for 21-OH deficiency. Therefore, this study is aimed at investigating the carrier frequency of common pseudogene derived CYP21A2 mutations in Southern India. Recently, a cost-effective Allele-specific PCR based genotyping for CYP21A2 hotspot mutations has been demonstrated to be a highly specific and sensitive assay at the authors' center. Leveraging this approach, a total of 1034 healthy individuals from South India underwent screening to identify the carrier frequency of nine hotspot mutations in the CYP21A2 gene. In this study, it was observed that 9.76% of the subjects were carriers for one or more of the nine different CYP21A2 mutations. Among the carriers, the most common was the large 30 kb deletion, followed by II72N, E6 CLUS, and I2G mutations. We have identified a high prevalence of CYP21A2 mutation carriers in Southern India. These findings emphasize the importance of implementing and expanding cost-effective genetic diagnostics and carrier screening throughout India. Such initiatives would play a crucial role in managing the disease burden, enabling early intervention, and establishing guidelines for CAH newborn genetic screening in the country. This study represents the first carrier screening data on CYP21A2 hotspot mutations from India and is the largest study conducted till date in this context.

Genetic Associations of Oral Clefts in Arabs.

This study aims to investigate genetic association between Non-syndromic Cleft lip with or without palate (NCLP) and 14 specific Single Nucleotide Polymorphism (SNPs) reported to be associated with NCLP from previous Genome Wide Association Studies (GWAS). A prospective case-control study. Ministry of Health (MOH) Cleft and Craniofacial Clinic and Kuwait University. One hundred sixty-four NCLP patients were recruited from MOH Cleft and Craniofacial clinic, and 491 controls from the Kuwait DNA bank established at Kuwait University. Total gDNA was extracted from whole blood withdrawn from patients and genotyped by real time PCR. Hardy-Weinberg Equilibrium was tested, and the set p value for significance (p < 0.05) was adjusted using the Benjamini - Hoochberg procedure to achieve 5% false discovery rate. Logistic regression multivariate analysis was used to test statistically significant differences between cases and controls. Genotyping both groups for the variants was determined through the allele discrimination software program. There was statistically significant difference between cases and controls in relation to two SNPs; LOC102724968 (rs13041247) (MAF cases/control = C (0.28/0.39) OR Homozygous = 1.30; 95% CI = 1.09-1.56, p = 0.0041) and PVT1 (rs987525) (MAF cases/control = A (0.41/0.27) OR heterozygous = 1.48; 95% CI =1.12-1.95, p = 0.0073), increasing the susceptibility to NCLP. Genetic variations are associated with the occurrence of oral clefts. Customized Next Generation Sequencing (NGS) panel to the Arab ethnicity is encouraged. In Addition, national preconception genetic carrier screening tests should expand to include common craniofacial anomalies.

Assessment of variant penetrance may improve the specificity of reproductive genetic carrier screening

Assessment of variant penetrance may improve the specificity of reproductive genetic carrier screening

Miscarriage risk assessment: a bioinformatic approach to identifying candidate lethal genes and variants

PurposeMiscarriage, often resulting from a variety of genetic factors, is a common pregnancy outcome. Preconception genetic carrier screening (PGCS) identifies at-risk partners for newborn genetic disorders; however, PGCS panels currently lack miscarriage-related genes. In this study, we evaluated the potential impact of both known and candidate genes on prenatal lethality and the effectiveness of PGCS in diverse populations.MethodsWe analyzed 125,748 human exome sequences and mouse and human gene function databases. Our goals were to identify genes crucial for human fetal survival (lethal genes), to find variants not present in a homozygous state in healthy humans, and to estimate carrier rates of known and candidate lethal genes in various populations and ethnic groups.ResultsThis study identified 138 genes in which heterozygous lethal variants are present in the general population with a frequency of 0.5% or greater. Screening for these 138 genes could identify 4.6% (in the Finnish population) to 39.8% (in the East Asian population) of couples at risk of miscarriage. This explains the cause of pregnancy loss in approximately 1.1–10% of cases affected by biallelic lethal variants.ConclusionThis study has identified a set of genes and variants potentially associated with lethality across different ethnic backgrounds. The variation of these genes across ethnic groups underscores the need for a comprehensive, pan-ethnic PGCS panel that includes genes related to miscarriage.

Exploring attitudes and experiences with reproductive genetic carrier screening among couples seeking medically assisted reproduction: a longitudinal survey study.

This study aimed to assess the attitudes and experiences of subfertile couples applying for medically assisted reproduction (MAR) using their own gametes towards reproductive genetic carrier screening (RGCS) for monogenic conditions. A prospective survey study was conducted where subfertile couples were recruited from the fertility centre of a university hospital in Flanders, Belgium. Participants were offered RGCS free of charge and completed self-administered questionnaires at three different time points. The study sample consisted of 26 couples. Most participants had no children, did not consider themselves as religious, and had some form of higher education. Overall, attitudes towards RGCS were mostly positive and the intention to participate in RGCS was high. Anxiety scores were only elevated and clinically relevant for a limited number of participants. A large proportion of participants would consider preventive reproductive options like prenatal diagnosis or in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) combined with pre-implantation genetic testing for monogenic conditions (PGT-M) in the event of an increased likelihood of conceiving a child with a hereditary condition. Participants were satisfied with their decision to undergo RGCS, and the majority would recommend RGCS to other couples. Our study findings suggest that subfertile couples applying for MAR using their own gametes find RGCS acceptable and have a positive attitude towards it. This study provides valuable insights into the perspectives of these couples, highlighting the need for appropriate counseling and timely information provision.

Carrier frequency estimation of pathogenic variants of autosomal recessive and X-linked recessive mendelian disorders using exome sequencing data in 1,642 Thais

BackgroundPeople with autosomal recessive disorders often were born without awareness of the carrier status of their parents. The American College of Medical Genetics and Genomics (ACMG) recommends screening 113 genes known to cause autosomal recessive and X-linked conditions in couples seeking to learn about their risk of having children with these disorders to have an appropriate reproductive plan.MethodsWe analyzed the exome sequencing data of 1,642 unrelated Thai individuals to identify the pathogenic variant (PV) frequencies in genes recommended by ACMG.ResultsIn the 113 ACMG-recommended genes, 165 PV and likely PVs in 60 genes of 559 exomes (34%, 559/1642) were identified. The carrier rate was increased to 39% when glucose-6-phosphate dehydrogenase (G6PD) was added. The carrier rate was still as high as 14.7% when thalassemia and hemoglobinopathies were excluded. In addition to thalassemia, hemoglobinopathies, and G6PD deficiency, carrier frequencies of > 1% were found for Gaucher disease, primary hyperoxaluria, Pendred syndrome, and Wilson disease. Nearly 2% of the couples were at risk of having offsprings with the tested autosomal recessive conditions.ConclusionsBased on the study samples, the expanded carrier screening, which specifically targeted common autosomal recessive conditions in Thai individuals, will benefit clinical outcomes, regarding preconception/prenatal genetic carrier screening.

Using a theory informed approach to design, execute, and evaluate implementation strategies to support offering reproductive genetic carrier screening in Australia

BackgroundHealth care professionals play a central role in offering reproductive genetic carrier screening but face challenges when integrating the offer into practice. The aim of this study was to design, execute, and evaluate theory-informed implementation strategies to support health care professionals in offering carrier screening.MethodsAn exploratory multi-method approach was systematically employed based on the Theoretical Domain Framework (TDF). Implementation strategies were designed by aligning TDF barriers reported by health care professionals involved in a large carrier screening study, to behaviour change techniques combined with study genetic counsellors’ experiential knowledge. The strategies were trialled with a subset of health care professionals and evaluated against controls, using findings from questionnaires and interviews with healthcare professionals. The primary outcome measure was the number of couples who initiated enrolment.ResultsHealth care professionals (n = 151) reported barriers in the TDF Domains of skills, e.g., lack of practice in offering screening, and challenges of environmental context and resources, e.g., lack of time, which informed the design of a skills video and a waiting room poster using the TDF-behaviour change technique linking tool. Following implementation, (Skills video n = 29 vs control n = 31 and Poster n = 46 vs control n = 34) TDF barrier scores decreased across all groups and little change was observed in the primary outcome measure. The skills video, though welcomed by health care professionals, was reportedly too long at seven minutes. The waiting room poster was seen as easily implementable.ConclusionsAs carrier screening moves towards mainstream healthcare, health care professionals report barriers to offering screening. To meet their needs, developing and testing experiential and theory-informed strategies that acknowledge contextual factors are essential.

The new face of cystic fibrosis in the era of population genetic carrier screening

BackgroundPopulation genetic carrier screening (PGCS) for cystic fibrosis (CF) has been offered to couples in Israel since 1999 and was included in a fully subsidized national program in 2008. We evaluated the impact of PGCS on CF incidence, genetic and clinical features. MethodsThis was a retrospective national study. Demographic and clinical characteristics of children with CF born in Israel between 2008 and 2018 were obtained from the national CF registry and from patients' medical records. Data on CF births, preimplantation genetic testing (PGT), pregnancy termination and de-identified data from the PGCS program were collected. ResultsCF births per 100,000 live births decreased from 8.29 in 2008 to 0.54 in 2018 (IRR = 0.84, p < 0.001). The CF pregnancy termination rate did not change (IRR = 1, p= 0.9) while the CF-related PGT rate increased markedly (IRR = 1.33, p < 0.001). One hundred and two children were born with CF between 2008 and 2018 with a median age at diagnosis of 4.8 months, range 0–111 months. Unlike the generally high uptake nationally, 65/102 had not performed PGCS. Even if all had utilized PGCS, only 51 would have been detected by the existing genetic screening panel. Clinically, 34 % of children were pancreatic sufficient compared to 23 % before 2008 (p = 0.04). ConclusionsSince institution of a nationwide PGCS program, the birth of children with CF decreased markedly. Residual function variants and pancreatic sufficiency were more common. A broader genetic screening panel and increased PGCS utilization may further decrease the birth of children with CF.

EP21.09: Reproductive genetic carrier screening and prenatal screening for normality: clinical utility and ethical concerns

EP21.09: Reproductive genetic carrier screening and prenatal screening for normality: clinical utility and ethical concerns

Preconceptionele uitgebreide dragerschapsscreening: een genetische test voor koppels met een kinderwens

Preconception expanded carrier screening: a genetic test for couples planning to conceive Approximately 1% to 2% of all couples have a risk of conceiving a child with a severe recessive disorder. Genetic expanded carrier screening (ECS) can determine this risk and allows couples planning a pregnancy to make informed reproductive choices. The Belgian genetic centers developed the ‘Belgian Genetic Expanded Carrier Screening’ (BeGECS), an ECS for 1,248 genes. The center for medical genetics (CMGG) of the Ghent University Hospital already received samples from over 350 couples. This article discusses the results of the first 250 analyses. Of the 250 couples, 70% consulted in the context of a preimplantation genetic testing (PGT) trajectory. These couples had an already known carriership in 1 or both partners of an autosomal dominant, autosomal recessive and/or X-linked disorder. These risks are of course not included in the results of the BeGECS analyses. The BeGECS analyses showed that 15 couples (6%) were at risk of having a child with an autosomal recessive disorder and 5 (2%) of having a child with a severe phenotype. In 7 couples (2.8%), 1 of the partners was carrier of an X-linked disorder. In 26% of those screened, individual carriership was identified for 1 of the highly frequent autosomal recessive disorders. Couples who are aware of this risk, prior to pregnancy, can make autonomous informed reproductive choices. To allow every couple to choose for ECS, it is essential that offering the test becomes part of standard preconception care.