Leveraging diverse genomic data to guide equitable carrier screening: Insights from gnomAD v.4.1.0.

Analysis of exome data from the latest release of the Genome Aggregation Database (gnomAD v.4.1.

Laboratory testing for preconception/prenatal carrier screening: A technical standard of the American College of Medical Genetics and Genomics (ACMG).

Carrier screening has historically assessed a relatively small number of autosomal recessive and X-linked conditions selected based on frequency in a specific subpopulation and association with severe morbidity or mortality. Advances in genomic technologies enable simultaneous screening of individuals for several conditions. The American College of Medical Genetics and Genomics recently published a clinical practice resource that presents a framework when offering screening for autosomal recessive and X-linked conditions during pregnancy and preconception and recommends a tier-based approach when considering the number of conditions to screen for and their frequency within the US population in general.

MRI Surveillance and Breast Cancer Mortality in Women With BRCA1 and BRCA2 Sequence Variations.

Importance: Magnetic resonance imaging (MRI) surveillance is offered to women with a pathogenic variant in the BRCA1 or BRCA2 gene who face a high lifetime risk of breast cancer. Surveillance with MRI is effective in downstaging breast cancers, but the association of MRI surveillance with mortality risk has not been well defined.

Objective: To compare breast cancer mortality rates in women with a BRCA1 or BRCA2 sequence variation who entered an MRI surveillance program with those who did not.

Labour induction for termination of pregnancy with severe fetal anomalies after 24 weeks' gestation: a case series and systematic review of the literature.

Purpose: Under some circumstances, individuals choose to undergo pregnancy termination for foetal anomalies in the second half of pregnancy. This report provides objective information on the clinical management of such cases and a systematic review of the literature on labour induction outcomes for third-trimester abortion using mifepristone-misoprostol.

Materials And Methods: The study is a case series describing outcomes for labour induction abortion for foetal anomalies, at gestational age 24 weeks and beyond.

Prenatal detection and evaluation of differences of sex development: A qualitative interview study of parental perspectives and unmet needs.

Objectives: Prenatal diagnoses of differences of sex development (DSD) are increasing due to availability of cell-free DNA screening (cell-free DNA screening (cfDNA)). This study explores first-hand experiences of parents whose children had prenatal findings of DSD.

Methods: Eligible parents were identified through chart review at a pediatric center and interviewed about their prenatal evaluation, decision making, informational sources, and support systems.

Screening for autosomal recessive and X-linked conditions during pregnancy and preconception: a practice resource of the American College of Medical Genetics and Genomics (ACMG).

Carrier screening began 50 years ago with screening for conditions that have a high prevalence in defined racial/ethnic groups (e.g., Tay-Sachs disease in the Ashkenazi Jewish population; sickle cell disease in Black individuals).

Pregnant Women's Perspectives on Expanded Carrier Screening.

Expanded carrier screening (ECS) is a relatively new carrier screening option that assesses many conditions simultaneously, as opposed to traditional ethnicity-based carrier screening for a limited number of conditions. This study aimed to explore pregnant women's perspectives on ECS, including reasons for electing or declining and anxiety associated with this decision-making. A total of 80 pregnant women were surveyed from Northwestern Medicine's Clinical Genetics Division after presenting for aneuploidy screening.

Expanded carrier screening: what the reproductive endocrinologist needs to know.

Expanded carrier screening refers to identification of carriers of single-gene disorders outside of traditional screening guidelines. New genetic testing technologies allow for such screening at costs that are comparable to single-gene testing. There is a high degree of variability among genetic testing laboratories as to the inclusion of different disorders, some of which have mild or unpredictable phenotypes.

Role of the 3-Vessel and Trachea View in Antenatal Detection of Tetralogy of Fallot.

Prenatal diagnosis of tetralogy of Fallot remains less frequent compared to other major congenital heart defects. In this study, we examined how often the 3-vessel and trachea view was abnormal in a large series of prenatally diagnosed cases of tetralogy of Fallot. In addition, we compared its sensitivity to that of the traditional outflow tract views for detection of tetralogy of Fallot.

Socioeconomic disparities in diagnostic testing after positive aneuploidy screening.

Objective: The objective of this study was to investigate the association between type of health insurance (Medicaid vs. private) and uptake of diagnostic testing for fetal aneuploidy after a positive screening test result.

Methods: We performed a retrospective cohort study of pregnant women who underwent aneuploidy screening in the first and/or second trimesters of pregnancy and received positive results.

3-D ultrasound of the fetal ear and fetal autosomal trisomies: a pilot study of a new screening protocol.

Objective: We hypothesize that the rotation of the ear in fetuses with common autosomal trisomies will be markedly different from euploid fetuses and amenable to detection by 3-D ultrasound in the render mode.

Methods: Study participants (10 weeks 4 days through 19 weeks 0 days) underwent a 3-D rendering of the fetal face and ear along with other biometric measurements prior to invasive testing.

Results: Of the 348 patients who underwent chorionic villi sampling (CVS) (n = 208) or amniocentesis (n = 140), 18 were diagnosed with trisomy 21, 4 with trisomy 18, and 1 with trisomy 13.

Carrier screening for cystic fibrosis.

Cystic fibrosis is the first genetic disorder for which universal screening of preconceptional or prenatal patients became a component of standard prenatal care. The molecular genetics and mutation profile of the CFTR gene are complex, with a wide range of phenotypic consequences. Carrier screening can facilitate risk assessment for prospective parents to have an affected offspring, although there remains a small residual risk for carrying a mutation even with a negative screening result.

Three-dimensional fast acquisition with sonographically based volume computer-aided analysis for imaging of the fetal heart at 18 to 22 weeks' gestation.

Objective: The purpose of this study was to determine how frequently cardiac images derived from 3-dimensional (3D) volume sets, acquired by fast acquisition and evaluated with sonographically based volume computer-aided analysis (sonoVCAD), were satisfactory for prenatal screening at 18 to 22 weeks' gestation.

Methods: A prospective study of 100 women with singleton pregnancies was undertaken. Three fast acquisition 3D volume sets were obtained from each patient.

Founder Fukutin mutation causes Walker-Warburg syndrome in four Ashkenazi Jewish families.

Objective: Walker-Warburg syndrome (WWS) is a genetically heterogeneous congenital muscular dystrophy caused by abnormal glycosylation of alpha-dystroglycan (alpha-DG) that is associated with brain malformations and eye anomalies. The Fukutin (FKTN) gene, which causes autosomal recessively inherited WWS is most often associated with Fukuyama congenital muscular dystrophy in Japan. We describe the clinical features of four nonconsanguinous Ashkenazi Jewish families with WWS and identify the underlying genetic basis for WWS.