Citations 2
Elective genomic sequencing for adults in research, clinical and commercial contexts
Linderman, Michael D. , Adelson, Sophia , Berro, Tala , Crawford, Scott , Cunningham, Tshaka J., Esplin, Edward D. , Ewing-Crawford, Altovise T, Nielsen, Daiva E. , Andrighetti, Heather, Bleyl, Steven B., Haverfield, Eden , Hegde, Madhuri , Konstantinos, Lazaridis N, Leonard, Debra G. B. , May, Thomas , McGinniss, Molly, Pandya, Vaibhav, Schadt, Eric E. , Zettler, Bethany , Team, PeopleSeq Study, Adelson, Sophia M , Berro, Tala M , Crawford, Scott D , Esplin, Edward D , Nielsen, Daiva E , Pereira, Stacey , Schmidlen, Tara , Haverfield, Eden V , Hegde, Madhuri , Kruszka, Paul , Leonard, Debra , May, Thomas , Schadt, Eric E , Tzovaras, Bastian Greshake , Zettler, Bethany , McGuire, Amy L , Green, Robert C. , Berro, Tala M., Anderson, Jennifer L., Cunningham, Tshaka, Ewing, Altovise T. , Nielsen, Daiva E., Church, George M. , Konstantinos, Lazaridis N., McGinniss, Molly A. , Schadt, Eric E., Green, Robert C., Juusola, Jane , McWalter, Kirsty , Esplin, Ed, Haverfield, Eden, Hazell, Allison, Gu, Jessica, Hogan, Jennifer, Church, George , Ball, Mad Price , McGinnis, Molly, Schadt, Eric, Linderman, Michael, McGuire, Amy, Christensen, Kurt D. , Caskey, Thomas, Zoltick, Emilie S. , Crawford, Scott, Young, Robert, Hunsanger, Jillian, Bradley, Sophia, Cunningham, Tshaka, Roberts, Scott, Ricks‐Santi, Luisel , Lillard, James, Washington, Kareem N., Johnson, Anthony
No container title available | June 19, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Purpose Elective genomic sequencing (EGS) returns monogenic disease findings in multiple genes, including potentially novel variants, and may also provide participants with carrier status, pharmacogenomic and other health-related information. The PeopleSeq Study assessed participants’ motivations for and concerns about EGS and the associated clinical and psychosocial outcomes across diverse EGS providers. Methods We administered a shared questionnaire to participants who chose to undergo EGS via 18 academic, clinical, or commercial EGS platforms. Results We enrolled 1575 participants, of whom 1147 (72.8%) completed a questionnaire after receiving their EGS results. A majority (60.3%) of the participants who completed a post-result questionnaire self-reported receiving results they assessed as important, including negative findings, and 75.9% reported a form of health-related utility. Among a subset (19.4%) who shared their EGS reports, 16.6% (37 of n =223) received a monogenic finding and self-reported results deemed “important” were consistent with EGS reports. Most participants (74.1%) discussed their results with their family, but fewer discussed their results with a healthcare provider other than the site team (41.7%) or had one or more medical visits as a direct result of their EGS testing (23.1%). Participants expressed diverse motivations for EGS, with 91.4% expressing interest in their personal disease risk and 54% who expressed quasi-indication-based motivations related to family medical history. Individuals motivated by family history reported important results at a significantly higher rate. Conclusions Early adopters of EGS are motivated by general interest in their health as well as quasi-indication-based considerations such as family history. A majority of participants learned results they considered medically important, but a much smaller segment engaged healthcare providers with their results.
A Genotype/Phenotype Study of KDM5B-Associated Disorders Suggests a Pathogenic Effect of Dominantly Inherited Missense Variants
Borroto, Maria Carla , Michaud, Coralie , Hudon, Chloé, Agrawal, Pankaj B. , Agre, Katherine , Applegate, Carolyn , Beggs, Alan H. , Callewaert, Bert , Chen, Mei-Jan, Curry, Cynthia J. , Devinsky, Orrin , Dudding‐Byth, Tracy , Fagan, K, Finnila, Candice R. , Gavrilova, Ralitza, Hiatt, Susan M. , Hildebrandt, Friedhelm , Wojcik, Monica H. , Kleefstra, Tjitske, Kolvenbach, Caroline M. , Korf, Bruce R. , Kruszka, Paul , Li, Hong , Litwin, Jessica, Marcadier, Julien , Platzer, Konrad , Blackburn, Patrick R. , Reijnders, Margot R.F. , Reutter, Heiko , Schanze, Ina, Shieh, Joseph T.C. , Stevens, Cathy A., Valivullah, Zaheer M. , Boogaard, Marie‐José H. van den , Klee, Eric W. , Campeau, Philippe M. , Applegate, Carolyn D , Callewaert, Bert , Devinsky, Orrin , Wojcik, Monica H , Kruszka, Paul , Platzer, Konrad , Reutter, Heiko , van den Boogaard, Marie-José , Klee, Eric W , Campeau, Philippe M , Beggs, Alan H , Björnsson, Hans T. , Genetti, Casie A. , Kleefstra, Tjitske
Genes | August 6, 2024 | Volume: 15 | Issue: 8 | Pages: 1033
Bi-allelic disruptive variants (nonsense, frameshift, and splicing variants) in KDM5B have been identified as causative for autosomal recessive intellectual developmental disorder type 65. In contrast, dominant variants, usually disruptive as well, have been more difficult to implicate in a specific phenotype, since some of them have been found in unaffected controls or relatives. Here, we describe individuals with likely pathogenic variants in KDM5B, including eight individuals with dominant missense variants. This study is a retrospective case series of 21 individuals with variants in KDM5B. We performed deep phenotyping and collected the clinical information and molecular data of these individuals’ family members. We compared the phenotypes according to variant type and to those previously described in the literature. The most common features were developmental delay, impaired intellectual development, behavioral problems, autistic behaviors, sleep disorders, facial dysmorphism, and overgrowth. DD, ASD behaviors, and sleep disorders were more common in individuals with dominant disruptive KDM5B variants, while individuals with dominant missense variants presented more frequently with renal and skin anomalies. This study extends our understanding of the KDM5B-related neurodevelopmental disorder and suggests the pathogenicity of certain dominant KDM5B missense variants.