Pharmacogenomic findings from clinical whole exome sequencing of diagnostic odyssey patients

被引:19
作者
Cousin, Margot A. [1 ,2 ]
Matey, Eric T. [1 ]
Blackburn, Patrick R. [3 ,4 ]
Boczek, Nicole J. [1 ,2 ]
McAllister, Tammy M. [1 ]
Kruisselbrink, Teresa M. [1 ]
Babovic-Vuksanovic, Dusica [1 ,5 ]
Lazaridis, Konstantinos N. [1 ,6 ]
Klee, Eric W. [1 ,2 ,5 ]
机构
[1] Mayo Clin, Ctr Individualized Med, Rochester, MN USA
[2] Mayo Clin, Dept Hlth Sci Res, 200 First St SW, Rochester, MN 55905 USA
[3] Mayo Clin, Ctr Individualized Med, Jacksonville, FL 32224 USA
[4] Mayo Clin, Dept Hlth Sci Res, Jacksonville, FL 32224 USA
[5] Mayo Clin, Dept Clin Gen, Rochester, MN USA
[6] Mayo Clin, Dept Gastroenterol, Rochester, MN USA
关键词
Exome sequencing; pediatric; pharmacogenomics; precision medicine; secondary findings; IMPLEMENTATION CONSORTIUM GUIDELINES; GENOMIC MEDICINE; SUPPORT; CYP2C9; EXPRESSION; KNOWLEDGE; GENOTYPES; VARIANTS; ONTOGENY; SYSTEM;
D O I
10.1002/mgg3.283
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background We characterized the pharmacogenomics (PGx) results received by diagnostic odyssey patients as secondary findings during clinical whole exome sequencing (WES) testing as a part of their care in Mayo Clinic's Individualized Medicine Clinic to determine the potential benefits and limitations to this cohort. Methods WES results on 94 patients included a subset of PGx variants in CYP2C19, CYP2C9, and VKORC1 if identified in the patient. Demographic, phenotypic, and medication usage information was abstracted from patient medical data. A pharmacist interpreted the PGx results in the context of the patients' current medication use and made therapeutic recommendations. Results The majority was young with a median age of 10 years old, had neurological involvement in the disease presentation (71%), and was currently taking medications (90%). Of the 94 PGx-evaluated patients, 91% had at least one variant allele reported and 20% had potential immediate implications on current medication use. Conclusion Due to the disease complexity and medication needs of diagnostic odyssey patients, there may be immediate benefit obtained from early life PGx testing for many and most will likely find benefit in the future. These results require conscientious interpretation and management to be actionable for all prescribing physicians throughout the lifetime of the patient.
引用
收藏
页码:269 / 279
页数:11
相关论文
共 50 条
[41]   Clinical Application of Genome and Exome Sequencing as a Diagnostic Tool for Pediatric Patients: a Scoping Review of the Literature [J].
Smith, Hadley Stevens ;
Swint, J. Michael ;
Lalani, Seema R. ;
Yamal, Jose-Miguel ;
Otto, Marcia C. de Oliveira ;
Castellanos, Stephan ;
Taylor, Amy ;
Lee, Brendan H. ;
Russell, Heidi V. .
GENETICS IN MEDICINE, 2019, 21 (01) :3-16
[42]   Measuring coverage and accuracy of whole-exome sequencing in clinical context [J].
Kong, Sek Won ;
Lee, In-Hee ;
Liu, Xuanshi ;
Hirschhorn, Joel N. ;
Mandl, Kenneth D. .
GENETICS IN MEDICINE, 2018, 20 (12) :1617-1626
[43]   Reporting Incidental Findings in Clinical Whole Exome Sequencing: Incorporation of the 2013 ACMG Recommendations into Current Practices of Genetic Counseling [J].
Smith, Lacey A. ;
Douglas, Jessica ;
Braxton, Alicia A. ;
Kramer, Kate .
JOURNAL OF GENETIC COUNSELING, 2015, 24 (04) :654-662
[44]   Pathogenic variants identification in primary congenital glaucoma patients using whole exome sequencing [J].
Ahmad, Shahzad ;
Gandapur, Muhammad Saleem ;
Jelani, Musharraf ;
Muhammad, Anees ;
Ul Haq, Ihtisham ;
Mahsood, Yousaf Jamal ;
Ahmad, Sajjad ;
Alonazi, Wadi B. ;
Bibi, Nousheen ;
Sarwar, Muhammad Tahir ;
Khan, Taj Ali .
SCIENTIFIC REPORTS, 2025, 15 (01)
[45]   Ending a diagnostic odyssey: Moving from exome to genome to identify cockayne syndrome [J].
Friedman, Jennifer ;
Bird, Lynne M. ;
Haas, Richard ;
Robbins, Shira L. ;
Nahas, Shareef A. ;
Dimmock, David P. ;
Yousefzadeh, Matthew J. ;
Witt, Mariah A. ;
Niedernhofer, Laura J. ;
Chowdhury, Shimul .
MOLECULAR GENETICS & GENOMIC MEDICINE, 2021, 9 (07)
[46]   Medically Actionable Secondary Findings from Whole-Exome Sequencing (WES) Data in a Sample of 3972 Individuals [J].
Melo, Mafalda ;
Ribeiro, Mariana ;
Silva, Paulo Filipe ;
Valente, Susana ;
Alves, Filipe ;
Venancio, Margarida ;
Sequeiros, Jorge ;
Freixo, Joao Parente ;
Antunes, Diana ;
Oliveira, Jorge .
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2025, 26 (08)
[47]   Secondary findings from whole-exome/genome sequencing evaluating stakeholder perspectives. A review of the literature [J].
Delanne, J. ;
Nambot, S. ;
Chassagne, A. ;
Putois, O. ;
Pelissier, A. ;
Peyron, C. ;
Gautier, E. ;
Thevenon, J. ;
Cretin, E. ;
Bruel, A. L. ;
Goussot, V. ;
Ghiringhelli, F. ;
Boidot, R. ;
Mau-Them, F. Tran ;
Philippe, C. ;
Vitobello, A. ;
Demougeot, L. ;
Vernin, C. ;
Lapointe, A. S. ;
Bardou, M. ;
Luu, M. ;
Binquet, C. ;
Lejeune, C. ;
Joly, L. ;
Juif, C. ;
Baurand, A. ;
Sawka, C. ;
Bertolone, G. ;
Duffourd, Y. ;
Sanlaville, D. ;
Pujol, P. ;
Genevieve, D. ;
Houdayer, F. ;
Thauvin-Robinet, C. ;
Faivre, L. .
EUROPEAN JOURNAL OF MEDICAL GENETICS, 2019, 62 (06)
[48]   The impact of reporting incidental findings from exome and whole-genome sequencing: predicted frequencies based on modeling [J].
Ding, Lucy-Enid ;
Burnett, Leslie ;
Chesher, Douglas .
GENETICS IN MEDICINE, 2015, 17 (03) :197-204
[49]   Whole exome sequencing of Rett syndrome-like patients reveals the mutational diversity of the clinical phenotype [J].
Mario Lucariello ;
Enrique Vidal ;
Silvia Vidal ;
Mauricio Saez ;
Laura Roa ;
Dori Huertas ;
Mercè Pineda ;
Esther Dalfó ;
Joaquin Dopazo ;
Paola Jurado ;
Judith Armstrong ;
Manel Esteller .
Human Genetics, 2016, 135 :1343-1354
[50]   Diagnostic yield of clinical exome sequencing in 868 children with neurodevelopmental disorders [J].
Neuens, Sebastian ;
Soblet, Julie ;
Penninckx, Aurelie ;
Detry, Claire ;
Badoer, Cindy ;
Desmyter, Laurence ;
Peyrassol, Xavier ;
Wilkin, Francoise ;
Busson, Adeline ;
Bruneau, Marie ;
Grenet, Marie-Laure ;
Le Morillon, Alice ;
Aeby, Alec ;
Deconinck, Nicolas ;
Prigogine, Cynthia ;
Monier, Anne ;
Juvene, Elodie ;
Balfroid, Tom ;
Van Hecke, Audrey ;
Christiaens, Florence ;
Depondt, Chantal ;
Brachet, Cecile ;
Delvenne, Veronique ;
Lufin, Nicolas ;
Bouysran, Youssef ;
Kammoun, Molka ;
Daneels, Dorien ;
Caljon, Ben ;
Croes, Didier ;
Olsen, Catharina ;
Van Dooren, Sonia ;
Migeotte, Isabelle ;
Vandernoot, Isabelle ;
Marangoni, Martina ;
Coppens, Sandra ;
Smits, Guillaume ;
Vilain, Catheline .
EUROPEAN JOURNAL OF MEDICAL GENETICS, 2025, 76