Preconception genetic screening

OBJECTIVES: To explore informed choice in reproductive genetic carrier screening (RGCS). METHODS: Women visiting a gynaecologist practice in Flanders (Belgium) were asked to consider participation in a study where RGCS was offered for free to them and their male partner. A modified Multidimensional Measure of Informed Choice was used to determine whether couples who opted for RGCS made an informed choice. In addition, we assessed risk perception, feelings towards RGCS, anxiety and decisional conflict...

Duchenne muscular dystrophy (DMD), an X-linked recessive condition is maternally inherited in two-thirds of affected boys. It is important to establish carrier status of female relatives to restore reproductive confidence for non-carriers and facilitate reproductive options and cardiac surveillance for carriers. This study investigates disease incidence within an Australian model of cascade screening and evolving genetic diagnostic technologies. A retrospective population-based cohort study of all genetically and/or histopathologically confirmed males with DMD, born in New South Wales and the Australian Capital Territory was undertaken from 2002-2012...

OBJECTIVE: Faster and cheaper next generation sequencing technologies have enabled expansion of carrier screening for recessive disorders, potentially facilitating population-based implementation regardless of ancestry or family history. Little is known however about the attitudes regarding population-based carrier screening among families with genetic disorders. This study assessed views among parents and patients with a recessive disorder and parents of a child with Down syndrome (DS) on expanded carrier screening (ECS)...

BACKGROUND: The American College of Obstetricians and Gynecologists recommends prenatal genetic testing (PGT) be offered to all pregnant persons regardless of known risk factors. However, significant racial/ethnic differences exist regarding acceptance of PGT contributing to disparities. Latinas (Latinx), one of the fastest growing ethnic groups in the United States, have low PGT acceptance rates. This systematic scoping review aimed to provide a landscape of existing literature on Latinx individuals' knowledge of, preferences for, and experiences with prenatal and preconception genetic testing...

PURPOSE: Genes associated with nonsyndromic hearing loss are commonly included in reproductive carrier screening panels, which are now routinely offered in preconception and prenatal care in many countries. However, there is debate whether hearing loss should be considered a medical condition appropriate for screening. This systematic review assessed research on opinions of those with a lived experience of deafness and the general public regarding genetic testing for deafness in the reproductive setting...

Expanded carrier screening (ECS) has become an increasingly common technique to assess the genetic risks of individuals in the prenatal or preconception period. Unexpected variants unrelated to referral are being increasingly detected in asymptomatic individuals through ECS. In this study, we reported an asymptomatic male with duplication of exons 56-61 in the DMD gene through ECS using whole-exome sequencing (WES), which was also detected in a male patient diagnosed with typical Duchenne muscular dystrophy (DMD)...

BACKGROUND: Founder populations that have recently undergone important genetic bottlenecks such as French-Canadians and Ashkenazi Jews can harbor some pathogenic variants at a higher carrier rate than the general population, putting them at a higher risk for certain genetic diseases. In these populations, there can be considerable benefit to performing ethnic-based or expanded preconception carrier screening, which can help in the prevention or early diagnosis and management of some genetic diseases...

Craniorachischisis totalis (anencephaly with total open spina bifida) is the most severe form of neural tube defects. The exact aetiology of neural tube defects remains poorly understood. We report a case of a primigravida in her 20s with a fetus in which craniorachischisis totalis was diagnosed during the first-trimester ultrasound at 11 weeks of gestation. The parents opted for pregnancy termination and the diagnosis was confirmed postnatally. Besides the lack of folic acid supplementation during preconception, no other risk factor was found...

Prenatal and preconception genetic counselors are trained to take patient pedigrees to evaluate for potential risks for genetic conditions, including hereditary cancer syndromes. However, little research has been published on how often prenatal/preconception genetic counselors provide recommendations for cancer genetic counseling solely based on a family history of cancer. Therefore, this study sought to (a) characterize the types of cancers recognized for a cancer genetic counseling recommendation, (b) analyze appointment indications associated with discussion documentation, and (c) investigate how often National Comprehensive Cancer Center (NCCN) genetic testing criteria for Hereditary Breast and Ovarian Cancer syndrome (HBOC) and Lynch syndrome were met and how often a recommendation for cancer genetic counseling was made...

Reproductive genetic carrier screening (RGCS) allows to identify couples who have an increased likelihood of conceiving a child affected with an autosomal recessive or X-linked monogenic condition. Multiple studies have reported on a wide and fragmented set of reasons to accept or decline RGCS. Only a few studies have been performed to assess the uptake of RGCS. Nonpregnant women visiting their gynecologist were invited to complete a questionnaire assessing perceived susceptibility, the acceptability of offering RGCS, attitudes, the intention to participate in RGCS, reasons to accept or decline RGCS, and sociodemographic characteristics...

Preconception carrier screening allows identification of couples at risk to have offspring with autosomal recessive and X-linked disorders. In a current multiethnic world, screening based on self-reported ancestry has limitations. Here we describe the findings of a comprehensive pan-ethnic variant-based carrier screening, using the Israeli Jewish population as a model. The cohort included 1696 individuals (848 couples) tested with the 'MyScreen' multigene panel. The panel covers 1206 variants spanning 385 genes, known in different Jewish ethnicities and local Arab, Druze and Bedouin populations...

PURPOSE: Adult-onset disease risks associated with carriers of recessive disease have and will continue to be identified. As carrier screening becomes more broadly utilized, providers face the dilemma of whether they should discuss these risks during discussions with prospective parents. This study aimed to understand whether preconception/prenatal genetic counselors (PPGCs) were aware of the risk of Parkinson disease in carriers of, and persons with, Gaucher disease and the reasons behind choosing whether to discuss this risk with patients...

PURPOSE: The Mexican Jewish community (MJC) is a previously uncharacterized, genetically isolated group composed of Ashkenazi and Sephardi-Mizrahi Jews who migrated in the early 1900s. We aimed to determine the heterozygote frequency of disease-causing variants in 302 genes in this population. METHODS: We conducted a cross-sectional study of the MJC involving individuals representing Ashkenazi Jews, Sephardi-Mizrahi Jews, or mixed-ancestry Jews. We offered saliva-based preconception pan-ethnic expanded carrier screening, which examined 302 genes...

OBJECTIVE: Between 2016 and 2017, a population-based preconception expanded carrier screening (PECS) test was developed in the Netherlands during a pilot study. It was subsequently made possible in mid-2018 for couples to ask to have such a PECS test from specially trained general practitioners (GPs). Research has described GPs as crucial in offering PECS tests, but little is known about the GPs' views on PECS and their experiences of providing this test. This article presents a thematic analysis of the PECS practice from the perspective of GPs and a bioethical discussion of the empirical results...

Background: Antenatally detected occipital encephalocele and polycystic kidneys are a common presentation of ciliopathies like Joubert syndrome and Meckel Gruber syndrome which have considerable genetic and phenotypic overlap. Case reports: We describe 3 cases of antenatally diagnosed occipital encephalocele and enlarged kidneys with fetal autopsy, histopathology & exome sequencing results. A novel nonsense variant in the CEP290 gene was reported in first case (Meckel syndrome). The second case shows the importance of fetal exome where the parents were carriers for 2 ciliopathy genes (TMEM138 & SDCCAG8)...

Genetic studies performed in consanguineous couples suggest that the reproductive risk that distinguish them from other couples in the general population is related to autosomal recessive (AR) diseases. This risk is scattered among the thousands of known and potential AR diseases. Thus, for effective preconceptional screening of consanguineous couples it is necessary a test that encompasses the largest number of genes possible. For that reason, we decided to create a protocol based on whole exome sequencing (WES)...

Background: Decidualization of the uterine mucosa drives the maternal adaptation to invasion by the placenta. Appropriate depth of placental invasion is needed to support a healthy pregnancy; shallow invasion is associated with the development of severe preeclampsia (sPE). Maternal contribution to sPE through failed decidualization is an important determinant of placental phenotype. However, the molecular mechanism underlying the in vivo defect linking decidualization to sPE is unknown...

BACKGROUND: Globally, about 6% of children are born with a serious birth defect of genetic or partially genetic origin. Carrier screening or testing is one way to identify couples at increased risk of having a child with an autosomal recessive condition. The most common autosomal recessive conditions are thalassaemia, sickle cell disease, cystic fibrosis and Tay-Sachs disease, with higher carrier rates in high-risk populations of specific ancestral backgrounds. Identifying and counselling couples at genetic risk of the conditions before pregnancy enables them to make fully informed reproductive decisions, with some of these choices not being available if testing is only offered in an antenatal setting...

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INTRODUCTION: Chromosomal abnormalities and monogenic disorders account for ~15%-25% of recognisable birth defects. With limited treatment options, preconception and prenatal screening were developed to reduce the incidence of such disorders. Currently, non-invasive prenatal screening (NIPS) for common aneuploidies is implemented worldwide with superiority over conventional serum or sonographic screening approaches. However, the clinical validity for the screening of frequent chromosome segmental copy number variations and monogenic disorders still awaits to be proved...