Article
Genetics & Heredity
Kelly M. Morgan, Jada G. Hamilton, Heather Symecko, Daniella Kamara, Colby Jenkins, Jenny Lester, Kelsey Spielman, Lydia E. Pace, Camila Gabriel, Jeffrey D. Levin, Prince Rainier Tejada, Anthony Braswell, Vanessa Marcell, Temima Wildman, Bryan Devolder, Robin Camhi Baum, Jeremy N. Block, Yuri Fesko, Kylin Boehler, Victoria Howell, Jacob Heitler, Mark E. Robson, Katherine L. Nathanson, Nadine Tung, Beth Y. Karlan, Susan M. Domchek, Judy E. Garber, Kenneth Offit
Summary: This study aimed to evaluate the uptake and follow-up of internet-assisted population genetic testing (GT) for BRCA1/2 Ashkenazi Jewish founder pathogenic variants (AJPVs). The study found that internet-enabled outreach can expand access to targeted GT and promote increased cancer screening among AJPV carriers.
GENETICS IN MEDICINE
(2022)
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
Multidisciplinary Sciences
Arnon Karni, Gil Ben Noon, Tamara Shiner, Ifat Vigiser, Hadar Kolb, Keren Regev
Summary: In Israel, Non-Ashkenazi Jewish patients have an earlier onset of disease, more severe disability, and a more balanced female-to-male ratio compared to Ashkenazi Jewish patients.
SCIENTIFIC REPORTS
(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
Genetics & Heredity
Monica Ziff, Juliette Harris
Summary: The unique British genetic carrier screening programme for individuals with Ashkenazi Jewish ancestry exemplifies a partnership between the NHS and charity Jnetics, providing affordable access to carrier screening and expanding outreach through community and social media campaigns. The model, implemented in various settings, offers free screening and has adapted to offer genetic screening virtually in response to the COVID-19 pandemic. The screening panel is being expanded to include other conditions in Jewish communities and aims to provide a model for genetically at-risk communities.
JOURNAL OF COMMUNITY GENETICS
(2022)
Article
Obstetrics & Gynecology
D. Reisel, M. Burnell, L. Side, K. Loggenberg, S. Gessler, R. Desai, S. Sanderson, A. F. Brady, H. Dorkins, Y. Wallis, C. Jacobs, R. Legood, U. Beller, I Tomlinson, J. Wardle, U. Menon, I Jacobs, R. Manchanda
Summary: Jewish religious and cultural identity, as well as denominational affiliation, do not seem to significantly influence interest, intention, or uptake of population-based BRCA testing. BRCA testing shows robust uptake across all Jewish denominations.
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
(2021)
Article
Genetics & Heredity
David A. Zeevi, Wendy K. Chung, Chaim Levi, Sholem Y. Scher, Rachel Bringer, Yael Kahan, Hagit Muallem, Rinat Benel, Yoel Hirsch, Tzvi Weiden, Ahron Ekstein, Josef Ekstein
Summary: This study provides carrier screening data for autosomal recessive pathogenic variants among Syrian Jews, showing that some individuals carry at least one pathogenic variant, supporting premarital genetic screening to reduce disease incidence.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Genetics & Heredity
Kevin T. Booth, Yoel Hirsch, Anna C. Vardaro, Josef Ekstein, Devorah Yefet, Adina Quint, Tzvi Weiden, David P. Corey
Summary: This study investigated the genetic causes of hearing loss in four Ashkenazi Jewish families, identifying new variants in the MYO15A gene. The research revealed the impact of different variants on the phenotype of hearing loss, further elucidating the role of genetic backgrounds in hearing loss.
FRONTIERS IN GENETICS
(2021)
Article
Genetics & Heredity
Eleanor Roberts, Elke M. van Veen, Helen Byers, Ofra Barnett-Griness, Naomi Gronich, Flavio Lejbkowicz, Mila Pinchev, Miriam J. Smith, Anthony Howell, William G. Newman, Emma R. Woodward, Elaine F. Harkness, Adam R. Brentnall, Jack Cuzick, Gad Rennert, Sacha J. Howell, D. . Gareth Evans
Summary: Polygenic risk scores (PRSs) are an important part of accurate breast cancer risk prediction, but they need to be calibrated for different ethnicities. This study found that commercially available PRSs, which assume that Ashkenazi Jewish (AJ) population is of White European (WE) origin, do not accurately predict breast cancer risk in AJ women due to differences in effect allele frequencies. It is necessary to recalibrate PRSs using AJ-specific effect allele frequencies.
GENETICS IN MEDICINE
(2023)
Article
Genetics & Heredity
Alessia Nasca, Ivano Di Meo, Yakov Fellig, Ann Saada, Orly Elpeleg, Daniele Ghezzi, Shimon Edvardson
Summary: Mutations in the MSTO1 gene can lead to a rare genetic disorder characterized by muscle and nerve impairment, resulting in muscle myopathy and cerebellar ataxia. The identified novel homozygous missense mutation in the MSTO1 gene was confirmed to play a pathogenic role in the development of the disease.
JOURNAL OF HUMAN GENETICS
(2021)
Article
Genetics & Heredity
Clara Estela Diaz-Velasquez, Rina Gitler, Adriana Antoniano, Ronny Kershenovich Sefchovich, Aldo Hugo De La Cruz-montoya, Hector Martinez-Gregorio, Ernesto Arturo Rojas-Jimenez, Ricardo Cortez Cardoso Penha, Luis Ignacio Terrazas, Talia Wegman-Ostrosky, Ephrat Levi-Lahad, Jovanny Zabaleta, Sandra Perdomo, Felipe Vaca-Paniagua
Summary: This study investigates the prevalence and composition of rare cancer predisposing germline variants in the Ashkenazi Jewish community of Mexico. It reveals a high carrier rate of pathogenic variants in high-risk genes and a diverse composition of pathogenic variants, suggesting the need for further research to assess the burden of hereditary breast cancer and implement appropriate preventative measures in this population.
FRONTIERS IN GENETICS
(2023)
Article
Oncology
Esther Forkosh, Michael Bergel, Kathryn E. Hatchell, Sarah M. Nielsen, Brandie Heald, Ariel A. Benson, Eitan Friedman, Edward D. Esplin, Lior H. Katz
Summary: This study investigates the prevalence of APC I1307K variant in Ashkenazi Jews and non-Ashkenazi Jewish white populations and assesses the risk of colorectal cancer and other cancers among carriers of this variant. The results show that non-Ashkenazi Jewish white individuals have a higher risk of various cancers, while Ashkenazi Jewish men are at a higher risk of cancer and melanoma.
Article
Genetics & Heredity
Hagai Levi, Shai Carmi, Saharon Rosset, Rinat Yerushalmi, Aviad Zick, Tamar Yablonski-Peretz, Qin Wang, Manjeet K. Bolla, Joe Dennis, Kyriaki Michailidou, Michael Lush, Thomas Ahearn, Irene L. Andrulis, Hoda Anton-Culver, Antonis C. Antoniou, Volker Arndt, Annelie Augustinsson, Paivi Auvinen, Laura Beane Freeman, Matthias Beckmann, Sabine Behrens, Marina Bermisheva, Clara Bodelon, Natalia Bogdanova, Stig E. Bojesen, Hermann Brenner, Helen Byers, Nicola Camp, Jose Castelao, Jenny Chang-Claude, Maria-Dolores Chirlaque, Wendy Chung, Christine Clarke, Margriet J. Collee, Sarah Colonna, Fergus Couch, Angela Cox, Simon S. Cross, Kamila Czene, Mary Daly, Peter Devilee, Thilo Dork, Laure Dossus, Diana M. Eccles, A. Heather Eliassen, Mikael Eriksson, Gareth Evans, Peter Fasching, Olivia Fletcher, Henrik Flyger, Lin Fritschi, Marike Gabrielson, Manuela Gago-Dominguez, Montserrat Garcia-Closas, Jose Angel Garcia-Saenz, Jeanine Genkinger, Graham G. Giles, Mark Goldberg, Pascal Guenel, Per Hall, Ute Hamann, Wei He, Peter Hillemanns, Antoinette Hollestelle, Reiner Hoppe, John Hopper, Simona Jakovchevska, Anna Jakubowska, Helena Jernstrom, Esther John, Nichola Johnson, Michael Jones, Joseph Vijai, Rudolf Kaaks, Elza Khusnutdinova, Cari Kitahara, Stella Koutros, Vessela Kristensen, Allison W. Kurian, James Lacey, Diether Lambrechts, Loic Le Marchand, Flavio Lejbkowicz, Annika Lindblom, Sibylle Loibl, Adriana Lori, Jan Lubinski, Arto Mannermaa, Mehdi Manoochehri, Dimitrios Mavroudis, Usha Menon, AnnaMarie Mulligan, Rachel Murphy, Ines Nevelsteen, William G. Newman, Nadia Obi, Katie O'Brien, Ken Offit, Andrew Olshan, Dijana Plaseska-Karanfilska, Janet Olson, Salvatore Panico, Tjoung-Won Park-Simon, Alpa Patel, Paolo Peterlongo, Brigitte Rack, Paolo Radice, Gad Rennert, Valerie Rhenius, Atocha Romero, Emmanouil Saloustros, Dale Sandler, Marjanka K. Schmidt, Lukas Schwentner, Mitul Shah, Priyanka Sharma, Jacques Simard, Melissa Southey, Jennifer Stone, William J. Tapper, Jack Taylor, Lauren Teras, Amanda E. Toland, Melissa Troester, Therese Truong, Lizet E. van der Kolk, Clarice Weinberg, Camilla Wendt, Xiaohong Rose Yang, Wei Zheng, Argyrios Ziogas, Alison M. Dunning, Paul Pharoah, Douglas F. Easton, Shay Ben-Sachar, Naama Elefant, Ron Shamir, Ran Elkon
Summary: This study examined the performance of European-based breast cancer (BC) polygenic risk score (PRS) models in Ashkenazi Jewish (AJ) women. The results showed that the European-based PRS models can identify AJ women with significantly increased BC risk, offering potential improvement in BC risk assessment for this population.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Biochemical Research Methods
Alissa L. Severson, Thorfinn Sand Korneliussen, Ida Moltke
Summary: In this study, a new probabilistic software tool called LocalNgsRelate is proposed for inferring identity-by-descent (IBD) sharing along the genome between pairs of individuals from low-depth Next Generation Sequencing (NGS) data. The method takes the uncertainty of genotype calling into account, leading to more accurate inference compared to existing methods. It is also shown to work well for NGS data down to a depth of 2x.
Article
Medical Laboratory Technology
Kuo Zhang, Guigao Lin, Jinming Li
Summary: Genetic carrier screening has been introduced 50 years ago and has since been improved. It now allows for multi-disease and pan-ethnic screening, although challenges remain in evaluating gene inclusion criteria, classifying the severity of genetic conditions, understanding clinical validity of gene-disease association and variant classification, and minimizing residual risks.
CLINICA CHIMICA ACTA
(2022)
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)