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Noninvasive cfDNA testing for monogenic disorders (sgNIPT) has become integrated into the care of pregnant women at increased risk based on carrier status, known family history, or ultrasound anomalies. The availability of commercial tests for common autosomal recessive and de novo autosomal dominant conditions has led to the use of these tests in low‐risk pregnancies. However, is the technology ready for use in this low‐risk population? This report is a summary of the debate on this topic at the 27th International Conference on Prenatal Diagnosis and Therapy. Both expert debaters provided strong arguments in favor and against the use of sgNIPT in low‐risk pregnancies. The argument in favor of sgNIPT for autosomal recessive conditions is that it allows the identification of affected pregnancies without the need for involving the partner in testing. Arguments for sgNIPT for autosomal dominant conditions include identification of affected fetuses that would have either presented later in pregnancy with fetal anomalies or not been detected prenatally given normal ultrasounds, respect for patient autonomy and patient desire for information. Strong arguments were made against offering sgNIPT screening. Given that traditional carrier screening for recessive conditions can be carried out in many jurisdictions, the added value of sgNIPT has not been clearly demonstrated. Arguments against sgNIPT for autosomal dominant conditions included the total lack of clinical validation studies and the risk of false reassurance in cases of negative results and unnecessary invasive procedures in cases of false positive results. Although there is a desire to take advantage of new technologies to improve the detection of monogenic disorders in low‐risk populations, based on the discussion and the audience vote, it appears premature to offer sgNIPT to all low risk pregnant women. Further clinical validation studies are needed prior to broad implementation. Key points: What's already known about this topic?cfDNA testing on maternal blood is technically possible and commercially available for dominant and recessive monogenic conditions. What does the study add?This report summarizes an oral debate presented at the 27th International Conference on Prenatal Diagnosis and Therapy in Edinburgh, UK on June 20th, 2023.The benefits, limitations and challenges of performing cfDNA screening for monogenic conditions in low‐risk populations are discussed. [ABSTRACT FROM AUTHOR]

PurposeThe endoplasmic reticulum-associated degradation pathway is responsible for the translocation of misfolded proteins across the endoplasmic reticulum membrane into the cytosol for subsequent degradation by the proteasome. To define the phenotype associated with a novel inherited disorder of cytosolic endoplasmic reticulum-associated degradation pathway dysfunction, we studied a series of eight patients with deficiency of N-glycanase 1.MethodsWhole-genome, whole-exome, or standard Sanger sequencing techniques were employed. Retrospective chart reviews were performed in order to obtain clinical data.ResultsAll patients had global developmental delay, a movement disorder, and hypotonia. Other common findings included hypolacrima or alacrima (7/8), elevated liver transaminases (6/7), microcephaly (6/8), diminished reflexes (6/8), hepatocyte cytoplasmic storage material or vacuolization (5/6), and seizures (4/8). The nonsense mutation c.1201A>T (p.R401X) was the most common deleterious allele.ConclusionNGLY1 deficiency is a novel autosomal recessive disorder of the endoplasmic reticulum-associated degradation pathway associated with neurological dysfunction, abnormal tear production, and liver disease. The majority of patients detected to date carry a specific nonsense mutation that appears to be associated with severe disease. The phenotypic spectrum is likely to enlarge as cases with a broader range of mutations are detected.

Genetic and genomic technologies can effectively diagnose numerous genetic disorders. Patients benefit when genetic counselling accompanies genetic testing and international guidelines recommend pre‐ and post‐test genetic counselling with genome‐wide sequencing. However, there is a gap in knowledge regarding the unique genetic counselling considerations with different types of genetic testing in the Neonatal Intensive Care Unit (NICU) and the Pediatric Intensive Care Unit (PICU). This scoping review was conducted to identify the gaps in care with respect to genetic counselling for infants/pediatric patients undergoing genetic and genomic testing in NICUs and PICUs and understand areas in need of improvement in order to optimize clinical care for patients, caregivers, and healthcare providers. Five databases (MEDLINE [Ovid], Embase [Ovid], PsycINFO [Ebsco], CENTRAL [Ovid], and CINHAL [Ebsco]) and grey literature were searched. A total of 170 studies were included and used for data extraction and analysis. This scoping review includes descriptive analysis, followed by a narrative account of the extracted data. Results were divided into three groups: pre‐test, post‐test, and comprehensive (both pre‐ and post‐test) genetic counselling considerations based on indication for testing. More studies were conducted in the NICU than the PICU. Comprehensive genetic counselling was discussed in only 31% of all the included studies demonstrating the need for both pre‐test and post‐test genetic counselling for different clinical indications in addition to the need to account for different cultural aspects based on ethnicity and geographic factors. [ABSTRACT FROM AUTHOR]

When genetic tests are not funded publicly, out‐of‐pocket (OOP) pay options may be discussed with patients. We evaluated trends in genetic testing and OOP pay for two publicly funded British Columbia clinical programs serving >12 000 patients/year (The Hereditary Cancer Program [HCP] and Provincial Medical Genetics Program [PMGP]) between 2015–2019. Linear and regression models were used to explore the association of OOP pay with patient demographic variables at HCP. An interrupted time series and linear and logistic regression models were used on PMGP data to examine the effect of a change in the funding body. The total number of tests completed through PMGP, and HCP increased by 260% and 320%, respectively. OOP pay increased at HCP by 730%. The mean annual income of patients who paid OOP at HCP was ≥$3500 higher than in the group with funded testing (p < 0.0001). The likelihood of OOP pay increased at PMGP before the funding body change (OR per month: 1.07; 95% CI: 1.04, 1.10); while this likelihood had an immediate 87% drop when the change occurred (OR: 0.13; 95% CI: 0.06, 0.32). Patients with higher incomes are more likely to pay OOP. Financial barriers can create disparities in clinical outcomes. Funding decisions have a significant impact on rate of OOP pay. [ABSTRACT FROM AUTHOR]