Dataset Information

Evaluation and classification of severity for 176 genes on an expanded carrier screening panel.

ABSTRACT: BACKGROUND:Disease severity is important when considering genes for inclusion on reproductive expanded carrier screening (ECS) panels. We applied a validated and previously published algorithm that classifies diseases into four severity categories (mild, moderate, severe, and profound) to 176 genes screened by ECS. Disease traits defining severity categories in the algorithm were then mapped to four severity-related ECS panel design criteria cited by the American College of Obstetricians and Gynecologists (ACOG). METHODS:Eight genetic counselors (GCs) and four medical geneticists (MDs) applied the severity algorithm to subsets of 176 genes. MDs and GCs then determined by group consensus how each of these disease traits mapped to ACOG severity criteria, enabling determination of the number of ACOG severity criteria met by each gene. RESULTS:Upon consensus GC and MD application of the severity algorithm, 68 (39%) genes were classified as profound, 71 (40%) as severe, 36 (20%) as moderate, and one (1%) as mild. After mapping of disease traits to ACOG severity criteria, 170 out of 176 genes (96.6%) were found to meet at least one of the four criteria, 129 genes (73.3%) met at least two, 73 genes (41.5%) met at least three, and 17 genes (9.7%) met all four. CONCLUSION:This study classified the severity of a large set of Mendelian genes by collaborative clinical expert application of a trait-based algorithm. Further, it operationalized difficult to interpret ACOG severity criteria via mapping of disease traits, thereby promoting consistency of ACOG criteria interpretation.

SUBMITTER: Arjunan A

PROVIDER: S-EPMC7540025 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evaluation and classification of severity for 176 genes on an expanded carrier screening panel.

Arjunan Aishwarya A Bellerose Holly H Torres Raul R Ben-Shachar Rotem R Hoffman Jodi D JD Angle Brad B Slotnick Robert Nathan RN Simpson Brittany N BN Lewis Andrea M AM Magoulas Pilar L PL Bontempo Kelly K Schulze Jeanine J Tarpinian Jennifer J Bucher Jessica A JA Dineen Richard R Goetsch Allison A Lazarin Gabriel A GA Johansen Taber Katherine K

Prenatal diagnosis 20200616 10

<h4>Background</h4>Disease severity is important when considering genes for inclusion on reproductive expanded carrier screening (ECS) panels. We applied a validated and previously published algorithm that classifies diseases into four severity categories (mild, moderate, severe, and profound) to 176 genes screened by ECS. Disease traits defining severity categories in the algorithm were then mapped to four severity-related ECS panel design criteria cited by the American College of Obstetricians ...[more]

PMID: 32474937

Similar Datasets

Project description:Study questionWhat are the sperm and egg donor rejection rates after expanded carrier screening (ECS)?Summary answerUsing an ECS panel looking at 46/47 genes, 17.6% of donors were rejected.What is known alreadyThe use of ECS is becoming commonplace in assisted reproductive technology, including testing of egg and sperm donors. Most national guidelines recommend rejection of donors if they are carriers of a genetic disease. If the use of ECS increases, there will be a decline in the number of donors available.Study design, size, durationA review of the current preconception ECS panels available to donors was carried out through an online search. The genetic testing results of donors from Cryos International were analysed to determine how many were rejected on the basis of the ECS.Participants/materials, setting, methodsData on gamete donors and their carrier status was provided by Cryos International, who screen donors using their own bespoke ECS panel. The ECS panels identified through the review were compared to the Cryos International panel and data.Main results and the role of chanceA total of 16 companies and 42 associated ECS panels were reviewed. There were a total of 2673 unique disorders covered by the panels examined, with a mean of 329 disorders screened. None of these disorders were common to all panels. Cryos International screen 46 disorders in males and 47 in females. From 883 candidate donors, 17.6% (155/883) were rejected based on their ECS result. Carriers of alpha-thalassaemia represented the largest proportion of those rejected (19.4%, 30/155), then spinal muscular atrophy (15.5%, 24/155) and cystic fibrosis (14.8%, 23/155).Limitations, reasons for cautionPanel information was found on company websites and may not have been accurate.Wider implications of the findingsThis study highlights the need for consistent EU regulations and guidelines that allow genetic matching of gamete donors to their recipients, preventing the need to reject donors who are known carriers. A larger ECS panel would be most beneficial; however, this would not be viable without matching of donors and recipients.Study funding/competing interest(s)No specific funding was obtained. J.C.H. is the founder of Global Women Connected, a platform to discuss women's health issues and the Embryology and PGD Academy, who deliver education in clinical embryology. She has been paid to give a lecture by Cryos in 2019. A-B.S. is an employee of Cryos International.Trial registration numberN/A.

Dataset Information

Evaluation and classification of severity for 176 genes on an expanded carrier screening panel.

Publications

Evaluation and classification of severity for 176 genes on an expanded carrier screening panel.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets