Editors: Donna E. Hansel, MD, PhD, division head of pathology and laboratory medicine, MD Anderson Cancer Center, Houston; James Solomon, MD, PhD, assistant professor, Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York; Erica Reinig, MD, assistant professor and medical director of molecular diagnostics, University of Wisconsin-Madison; Marcela Riveros Angel, MD, molecular genetic pathology fellow, Department of Pathology, Oregon Health and Science University, Portland; Maedeh Mohebnasab, MD, assistant professor of pathology, University of Pittsburgh; Alicia Dillard, MD, associate clinical laboratory director, Omniseq/Labcorp, Buffalo, NY; and Richard Wong, MD, PhD, assistant professor of pathology, University of California San Diego.
Lived experience with genetic disease: significance relative to understanding severity
May 2025—As genomic technology and scientific knowledge advance, so too do their applications in health care. Clinical genetic testing, preimplantation genetic diagnosis (PGD), and heritable human genome editing (HHGE) are an ever-growing and evolving part of genomic medicine. The author explored the significance of lived experiences with genetic disease relative to understanding the severity or seriousness of such diseases in the genomic age. She focused on severity of disease, perceptions of symptoms of disease or associations with disease, and interplay between symptoms of disease and associations with disease. The data presented were collected as part of a larger mixed-methods research project exploring factors that influence attitudes toward the use of HHGE as a potential reproductive choice in the United Kingdom and how identifying those factors could aid the design of future regulations. Participants provided informed consent and were affected by a monogenic condition licensed for prevention by preimplantation genetic testing (PGT) in the United Kingdom. In-depth, structured interviews were conducted and consisted of open-ended questions, polls, and a ranking activity. Twenty-one adults aged 20 to 58 years were selected to participate in the research. Among the monogenic conditions represented in the pool of participants were beta thalassemia, germline BRCA2 mutation, cystic fibrosis, Huntington’s disease, muscular dystrophy, and Schwachman–Diamond syndrome. In one data set, participants ranked what they thought were the most impactful symptoms of disease or associations with disease. Pain and dependency were ranked first and second, respectively, in a list of nine disease symptoms or associations. Physiological degeneration and physiological impairments were ranked the least impactful, with scores of eight and nine, respectively. Several participants shared that trying to rank disease symptoms or associations was difficult because they often do not occur in isolation. One participant stated, “When I lose my independence, that affects me horrendously psychologically. But the loss of independence comes from all these things getting worse, so I think in a way there isn’t an order for them.” Participants indicated that the severity of a disease should be taken into account when considering potential applications for HHGE. They also responded that only severe diseases should be prevented via potential clinical genomic technologies. However, the author noted that no global definition of serious or severe exists in the context of disease. A report from the International Commission on the Clinical Use of HHGE (in conjunction with other recommendations) recommended that any initial applications of HHGE for reproductive purposes be limited to serious monogenic diseases. The report defined serious monogenic diseases as those that cause severe morbidity or premature death. Current frameworks to assess the severity of a genomic disease tend to focus on objective, biomedical factors of the condition and quality-adjusted life years. This article highlights that the concept of severity is entwined with the concept of quality of life and that some conditions may not seem severe to those who live with them.
Kaur A. Severity in the genomic age: the significance of lived experience to understandings of severity. Eur J Hum Genet. 2025;33:176–181.
Correspondence: Dr. Amarpreet Kaur at a.kaur.11@bham.ac.uk