Article
Health Care Sciences & Services
Sofia Morberg Jamterud, Anke Snoek
Summary: This article examines the information on preconception expanded carrier screening (PECS) on Dutch websites using multimodal critical discourse analysis. The study identifies three main discourses and subject positions related to risk and the couple, scientific facts and rational conceivers, and severity of conditions and responsible couples. The study highlights the importance of acknowledging the interrelation between epistemology and ethics in the discourse on PECS, and suggests that the focus on scientific facts in information on PECS may make existential and ethical dilemmas and choices invisible.
Article
Genetics & Heredity
Paranchai Boonsawat, Anselm H. C. Horn, Katharina Steindl, Alessandra Baumer, Pascal Joset, Dennis Kraemer, Angela Bahr, Ivan Ivanovski, Elena M. Cabello, Michael Papik, Markus Zweier, Beatrice Oneda, Pietro Sirleto, Tilo Burkhardt, Heinrich Sticht, Anita Rauch
Summary: This study investigated the potential of preconception expanded carrier screening (ECS) to reduce the risk of neurodevelopmental disorders (NDDs). The results showed that the risk reduction potential was up to 43.5% for consanguineous couples and 5.1% for nonconsanguineous couples. However, the study found that underestimation of pathogenicity and other factors compromised the risk reduction potential. Therefore, it is recommended to screen for genetic mutations in all couples seeking ECS and set sensible pathogenicity thresholds to optimize clinical outcomes.
NPJ GENOMIC MEDICINE
(2022)
Article
Genetics & Heredity
Bella Davidov, Amit Levon, Hadas Volkov, Naama Orenstein, Racheli Karo, Inbal Fatal Gazit, Nurit Magal, Lina Basel-Salmon, Michal Golan Mashiach
Summary: This study used the Israeli Jewish population as a model to conduct carrier screening and confirmed the advantages of variant-based comprehensive screening in detecting carriers and at-risk couples in a diverse population.
Article
Obstetrics & Gynecology
Julia Silver, Mary E. Norton
Summary: The use of expanded carrier screening, which can test for hundreds of genetic disorders at the same time, presents challenges and complexities due to the limited knowledge of genetic sequencing among front-line obstetric health care professionals. Urgent attention is required to address issues such as reclassification of variants, pretest and posttest counseling, and the responsibilities of health care professionals in ensuring patients understand the process of variant interpretation.
OBSTETRICS AND GYNECOLOGY
(2021)
Article
Genetics & Heredity
Dan Morgenstern-Kaplan, Jaime Raijman-Policar, Sore Majzner-Aronovich, Swaroop Aradhya, Daniel E. Pineda-Alvarez, Monica Aguinaga, Edna Elisa Garcia-Vences
Summary: This study aimed to determine the heterozygote frequency of disease-causing variants in the Mexican Jewish community (MJC). The results showed that 72.1% of participants carried at least one severe disease-causing variant in the analyzed genes. The most common genes with severe disease-causing variants were CFTR, MEFV, WNT10A, and GBA. Comparison with the Genome Aggregation Database (gnomAD) revealed statistically significant differences in variant frequencies. Additionally, 6% of couples were at risk of having a child with a severe disorder. The study highlights the importance of using carrier screening in the MJC and other understudied populations to facilitate informed decision-making for parents.
GENETICS IN MEDICINE
(2022)
Article
Genetics & Heredity
Liya Rabkina, Amy Swanson, Sharon Aufox, Lauren Propst, Morris Fiddler, Andrew Wagner, Aishwarya Arjunan
Summary: The study found that the majority of women before pregnancy had a certain awareness and interest in expanded carrier screening (ECS), which was mainly obtained through family, friends or independent online research. Their interest in ECS was primarily driven by the desire to make informed decisions about future pregnancies and to seek further confirmation.
PRENATAL DIAGNOSIS
(2021)
Article
Medicine, General & Internal
Sofia Morberg Jamterud, Anke Snoek, I. M. van Langen, Marian Verkerk, Kristin Zeiler
Summary: The study focuses on the development and implementation of population-based preconception expanded carrier screening (PECS) test in the Netherlands and its provision by general practitioners (GPs). The thematic analysis of interviews with 7 Dutch GPs highlights the complexity of choice on PECS and the need for shared decision-making within couples, as well as the existential concerns prompted by PECS. The bioethical discussion emphasizes the importance of training GPs in shared decision-making and addressing existential issues raised by genetic considerations.
Article
Genetics & Heredity
Andrea Busnelli, Oriana Ciani, Silvia Caroselli, Matteo Figliuzzi, Maurizio Poli, Paolo Emanuele Levi-Setti, Rosanna Tarricone, Antonio Capalbo
Summary: This study aimed to evaluate the cost-effectiveness of expanded carrier screening (ECS) compared with no screening in Italy. The results showed that all three ECS panels would be more cost-effective than no screening from the perspective of the Italian universal health care system.
GENETICS IN MEDICINE
(2023)
Article
Genetics & Heredity
Tirtza S. Strauss, Emily Schneider, Emily Boniferro, Erika Brockhoff, Anna Johnson, Guillaume Stoffels, Kristina Feldman, Olivia Grubman, David Cole, Farrah Hussain, Graham Ashmead, Zainab Al-ibraheemi, Lois Brustman
Summary: This study aimed to evaluate the rates, time, and barriers to complete expanded carrier screening (ECS) in prenatal patients. It found significant barriers to completion, including suboptimal patient follow-up and low partner screening rates.
GENETICS IN MEDICINE
(2023)
Article
Obstetrics & Gynecology
A. Capalbo, M. Fabiani, S. Caroselli, M. Poli, L. Girardi, C. Patassini, F. Favero, D. Cimadomo, A. Vaiarelli, C. Simon, L. F. Rienzi, F. M. Ubaldi
Summary: The preconception Expanded Carrier Screening (ECS) shows clinical utility and effectiveness in managing prospective parents, especially in improving couples' genetic risk assessment and avoiding detectable inheritable genetic offspring. The study results demonstrate that ECS can significantly impact reproductive planning and decision-making for at-risk couples.
HUMAN REPRODUCTION
(2021)
Review
Genetics & Heredity
James D. Goldberg, Summer Pierson, Katherine Johansen Taber
Summary: Carrier screening is a test that evaluates the reproductive risk of couples by testing for affected genes. Recent evidence shows that offering carrier screening to all patients, regardless of ethnicity, effectively identifies at-risk couples and is supported by professional guidelines. Based on evaluation, we recommend a core panel of 64 conditions to improve the number of patients receiving comprehensive carrier screening.
PRENATAL DIAGNOSIS
(2023)
Article
Genetics & Heredity
Anna Abuli, Mar Costa-Roger, Marta Codina-Sola, Irene Valenzuela, Jordi Leno-Colorado, Eulalia Rovira-Moreno, Anna Cueto-Gonzalez, Paula Fernandez-Alvarez, Elena Garcia-Arumi, Ivon Cusco, Eduardo F. Tizzano
Summary: Background: Consanguineous couples have an increased risk of severe diseases in offspring due to autosomal recessive disorders. Exome sequencing (ES) offers the possibility of extensive preconception carrier screening (PCS) in consanguineous couples who may be at risk of rare genetic disorders. Methods: We retrospectively analysed ES data from 65 probands affected with rare genetic disorders born from consanguineous couples, exploring diagnostic yield and carrier status for recessive disorders.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Obstetrics & Gynecology
Guido de Wert, Sanne van der Hout, Mariette Goddijn, Rita Vassena, Lucy Frith, Nathalie Vermeulen, Ursula Eichenlaub-Ritter
Summary: Expanded carrier screening is being increasingly offered to patients seeking assisted reproduction, raising ethical concerns regarding the professional responsibilities and potential benefits and harms of such screenings. Some European fertility clinics already provide preconception ECS, prompting a need for ethical guidance in this area. Patients undergoing assisted reproduction may have a particular interest in preconception ECS due to the burdens they already face, leading to unique ethical questions that require consideration.
HUMAN REPRODUCTION OPEN
(2021)
Article
Genetics & Heredity
Sarah Jurgensmeyer, Sarah Walterman, Andrew Wagner, Kenny Wong, Annie Bao, Sarah Stueber, Sara Spencer
Summary: The study found that male partners attending female carriers' screening appointments can increase the likelihood of them going through screening. Logical factors had more impact on males pursuing screening. On the other hand, female carriers reported that their male partners did not undergo screening mainly due to perceived low risk and lack of concern for the specific condition.
JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
(2021)
Article
Genetics & Heredity
Rivka Birnbaum, Shlomit Ezer, Nava Shaul Lotan, Avital Eilat, Keren Sternlicht, Lilach Benyamini, Orit Reish, Tzipora Falik-Zaccai, Gali Ben-Gad, Raya Rod, Reeval Segel, Katherine Kim, Barabra Burton, Catherine E. Keegan, Mallory Wagner, Lindsay B. Henderson, Nofar Mor, Ortal Barel, Yoel Hirsch, Vardiella Meiner, Orly Elpeleg, Tamar Harel, Hagar Mor-Shakad
Summary: A study identified a homozygous founder variant in the SGSM3 gene in individuals with neurodevelopmental disorders (NDDs) and short stature, establishing a connection between SGSM3 and NDDs. Further research is needed to understand the specific molecular mechanisms by which SGSM3 influences neurodevelopment and growth regulation.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Lily Agranat-Tamir, Shamam Waldman, Mario A. S. Martin, David Gokhman, Nadav Mishol, Tzilla Eshel, Olivia Cheronet, Nadin Rohland, Swapan Mallick, Nicole Adamski, Ann Marie Lawson, Matthew Mah, Megan Michel, Jonas Oppenheimer, Kristin Stewardson, Francesca Candilio, Denise Keating, Beatriz Gamarra, Shay Tzur, Mario Novak, Rachel Kalisher, Shlomit Bechar, Vered Eshed, Douglas J. Kennett, Marina Faerman, Naama Yahalom-Mack, Janet M. Monge, Yehuda Govrin, Yigal Erel, Benjamin Yakir, Ron Pinhasi, Shai Carmi, Israel Finkelstein, Liran Carmel, David Reich
Article
Biochemistry & Molecular Biology
Hila Fridman, Concetta Bormans, Moshe Einhorn, Daniel Au, Arjan Bormans, Yuval Porat, Luisa Fernanda Sanchez, Brent Manning, Ephrat Levy-Lahad, Doron M. Behar
Summary: The study compared the performance of Sanger sequencing with exome sequencing in gene detection, finding overall high concordance but presence of false-positive and false-negative results in both methods. Specific diagnosis should be highly suspected regardless of negative results from either Sanger sequencing or NGS.
MOLECULAR GENETICS AND GENOMICS
(2021)
Article
Ecology
Alissa L. Severson, Shai Carmi, Noah A. Rosenberg
Summary: Recent modeling studies have investigated the connection between runs of homozygosity (ROH), identity by descent (IBD), and pairwise coalescence times. The study examines various features of pairwise coalescence times in consanguinity models and introduces a separation-of-time-scales approach to analyze coalescence-time distributions. The results suggest that the consanguinity model behaves similarly to a standard coalescent, providing potential for predicting ROH and IBD in diploid populations based on demographic parameters.
THEORETICAL POPULATION BIOLOGY
(2021)
Article
Genetics & Heredity
Hila Fridman, Helger G. Yntema, Reedik Magi, Reidar Andreson, Andres Metspalu, Massimo Mezzavila, Chris Tyler-Smith, Yali Xue, Shai Carmi, Ephrat Levy-Lahad, Christian Gilissen, Han G. Brunner
Summary: Genome sequencing revealed that each individual in the European population carries at least 2 pathogenic variants, with nearly 1% of European couples facing the risk of having a child with a severe genetic disorder. The risk is significantly higher for first cousins and particularly increased for skeletal disorders and intellectual disabilities due to their unique genetic architecture.
AMERICAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Neurosciences
Todd Lencz, Jin Yu, Raiyan Rashid Khan, Erin Flaherty, Shai Carmi, Max Lam, Danny Ben-Avraham, Nir Barzilai, Susan Bressman, Ariel Darvasi, Judy H. Cho, Lorraine N. Clark, Zeynep H. Gumus, Joseph Vijai, Robert J. Klein, Steven Lipkin, Kenneth Offit, Harry Ostrer, Laurie J. Ozelius, Inga Peter, Anil K. Malhotra, Tom Maniatis, Gil Atzmon, Itsik Pe'er
Summary: Identification of rare variants associated with schizophrenia is challenging due to genetic heterogeneity, but in the Ashkenazi Jewish population, cases were found to have a higher frequency of novel MisLoF URVs compared to controls. The burden of MisLoF URVs was inversely correlated with polygenic risk scores in cases. The cadherin gene set was associated with schizophrenia, with a recurrent case mutation in PCDHA3 being linked to cytoplasmic aggregation formation.
Article
Multidisciplinary Sciences
Elena Arciero, Sufyan A. Dogra, Daniel S. Malawsky, Massimo Mezzavilla, Theofanis Tsismentzoglou, Qin Qin Huang, Karen A. Hunt, Dan Mason, Saghira Malik Sharif, David A. van Heel, Eamonn Sheridan, John Wright, Neil Small, Shai Carmi, Mark M. Iles, Hilary C. Martin
Summary: The research uncovered a strong recent population structure among British Pakistanis, influenced by the Biraderi social stratification system. All subgroups had low recent effective population sizes, with extensive identity-by-descent sharing and homozygosity increasing the risk of recessive disorders. The impact of cultural practices on Pakistani population structure and genomic diversity was highlighted, with implications for medical genetic studies.
NATURE COMMUNICATIONS
(2021)
Editorial Material
Oncology
Sari Lieberman, Hadar Goldvaser, Ephrat Levy-Lahad
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Ecology
Daniel J. Cotter, Alissa L. Severson, Shai Carmi, Noah A. Rosenberg
Summary: The presence of consanguineous unions reduces coalescence times in a population, and different types of first-cousin consanguinity have varying effects on the coalescence time distribution.
THEORETICAL POPULATION BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shamam Waldman, Daniel Backenroth, Eadaoin Harney, Stefan Flohr, Nadia C. Neff, Gina M. Buckley, Hila Fridman, Ali Akbari, Nadin Rohland, Swapan Mallick, Inigo Olalde, Leo Cooper, Ariel Lomes, Joshua Lipson, Jorge Cano Nistal, Jin Yu, Nir Barzilai, Inga Peter, Gil Atzmon, Harry Ostrer, Todd Lencz, Yosef E. Maruvka, Maike Lammerhirt, Alexander Beider, Leonard Rutgers, Virginie Renson, Keith M. Prufer, Stephan Schiffels, Harald Ringbauer, Karin Sczech, Shai Carmi, David Reich
Summary: We obtained genome-wide data from 33 Ashkenazi Jews dating back to the 14th century, and found that they are genetically similar to modern Ashkenazi Jews but show more variability in their Eastern European-related ancestry. The study also reveals that the ancient Ashkenazi Jewish community had already experienced a significant reduction in size, indicating substructure in medieval Ashkenazi Jews.
Article
Oncology
Rachel Michaelson-Cohen, Matan J. Cohen, Carmit Cohen, Dan Greenberg, Amir Shmueli, Sari Lieberman, Ariela Tomer, Ephrat Levy-Lahad, Amnon Lahad
Summary: This study analyzed the cost-effectiveness of BRCA mutation screening in the Ashkenazi Jewish population and found that population screening is both effective and cost-effective for preventing breast and ovarian cancer. BRCA testing should be made available to all Ashkenazi Jewish women, regardless of family history.
Meeting Abstract
Biochemistry & Molecular Biology
Hila Fridman, Helger G. Yntema, Reedik Magi, Reidar Andreson, Andres Metspalu, Massimo Mezzavila, Chris Tyler-Smith, Yali Xue, Shai Carmi, Ephrat Levy-Lahad, Christian Gilissen, Han G. Brunner
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Ophthalmology
Michelle Grunin, Gala Beykin, Elior Rahmani, Regev Schweiger, Gal Barel, Shira Hagbi-Levi, Sarah Elbaz-Hayoun, Batya Rinsky, Michal Ganiel, Shai Carmi, Eran Halperin, Itay Chowers
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2020)
Article
Genetics & Heredity
Katerina S. Kucera, Beth Lincoln Boyea, Brooke Migliore, Sarah Nelson Potter, Veronica R. Robles, Oksana Kutsa, Heidi Cope, Katherine C. Okoniewski, Anne Wheeler, Catherine W. Rehder, Edward C. Smith, Holly L. Peay
Summary: Screening for elevated CK-MM levels in dried blood spots is a feasible method to identify newborns with DMD. Including specific cutoffs, repeat testing, and genetic sequencing can improve the accuracy and sensitivity of screening.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Madeline Currey, Ilana Solomon, Sarah Mcgraw, Jenny Shen, Francisco Munoz, Ernesto Sosa, Vanessa Puello-Lozano, Sam Wing, Lisa Lopez, Michelle Afkhami, Janine Lobello, Szabolcs Szelinger, Stacy W. Gray
Summary: This study conducted qualitative interviews with cancer patients and providers to identify gaps in clinical care and propose care delivery solutions for the return of secondary germline findings. The responses of patients varied depending on the amount of pre-test counseling they received, and providers identified insufficient clinic time as a major barrier to pretest education. Online support tools and standardized pre-test education models were favored by providers. There were differing perspectives on how pre-test education should be integrated into clinical workflows, but agreement on the inclusion of differences between somatic and germline testing, likelihood of medically actionable findings, and the possibility of being referred to a genetics provider.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kiely N. James, Shimul Chowdhury, Yan Ding, Sergey Batalov, Kelly Watkins, Yong Hyun Kwon, Lucitia Van Der Kraan, Katarzyna Ellsworth, Stephen F. Kingsmore, Lucia Guidugli
Summary: This study used genome sequencing to detect a wide range of copy-number variants (CNVs) and other non-single nucleotide variant/indel variant types. These genetic alterations accounted for 15.8% of reported variants, with deletions being the most common type. The study also found that additional genetic tests were ordered in some cases, but failed to report the variants detected by genome sequencing.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Asem Berkalieva, Nicole R. Kelly, Ashley Fisher, Samuel F. Hohmann, Monisha Sebastin, Miranda Di Biase, Katherine E. Bonini, Priya Marathe, Jacqueline A. Odgis, Sabrina A. Suckiel, Michelle A. Ramos, Rosamond Rhodes, Noura S. Abul-Husn, John M. Greally, Carol R. Horowitz, Melissa P. Wasserstein, Eimear E. Kenny, Bruce D. Gelb, Bart S. Ferket
Summary: The study aims to understand the effects of returning diagnostic sequencing results on clinical actions and economic outcomes for pediatric patients with suspected genetic disorders. The results showed that patients with positive findings were more likely to receive specialist consultation, but there were no significant increases in overall physician services and costs. More large-scale studies are needed to confirm these findings.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kirstine Stochholm, Camilla Holmgard, Shanlee M. Davis, Claus H. Gravholt, Agnethe Berglund
Summary: This study assessed the incidence, prevalence, and age at diagnosis of individuals with 45,X/46,XY mosaicism and described the associated mortality pattern. The study found an increasing incidence of 45,X/46,XY mosaicism in males and a stable incidence in females. Males were diagnosed at an older age than females. Additionally, 45,X/46,XY mosaicism was associated with increased all-cause mortality.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Yunjia Chen, Ender Karaca, Nathaniel H. Robin, Dana Goodloe, Ali Al-Beshri, S. Joy Dean, Anna C. E. Hurst, Andrew J. Carroll, Fady M. Mikhail
Summary: This study confirms the association between DLG2 intragenic deletions and neurodevelopmental disorders, supports the haploinsufficiency of the DLG2 gene, and suggests a potential association between these deletions and congenital anomalies and dysmorphism.
GENETICS IN MEDICINE
(2024)