Pharmacogenomic Findings from Clinical Whole Exome Sequencing of Diagnostic Odyssey Patients

Overview

Journal Mol Genet Genomic Med

Specialty Genetics

Date 2017 May 27

PMID 28546997

Citations 14

Authors

Margot A Cousin

Eric T Matey

Patrick R Blackburn

Nicole J Boczek

Tammy M McAllister

Teresa M Kruisselbrink

Dusica Babovic-Vuksanovic

Konstantinos N Lazaridis

Eric W Klee

Affiliations

Soon will be listed here.

Abstract

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 ,, and 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.

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References

Fakhro K, Staudt M, Ramstetter M, Robay A, Malek J, Badii R . The Qatar genome: a population-specific tool for precision medicine in the Middle East. Hum Genome Var. 2016; 3:16016. PMC: 4927697. DOI: 10.1038/hgv.2016.16. View

Treluyer J, Benech H, Colin I, Pruvost A, Cheron G, Cresteil T . Ontogenesis of CYP2C-dependent arachidonic acid metabolism in the human liver: relationship with sudden infant death syndrome. Pediatr Res. 2000; 47(5):677-83. DOI: 10.1203/00006450-200005000-00020. View

Weinshilboum R . Inheritance and drug response. N Engl J Med. 2003; 348(6):529-37. DOI: 10.1056/NEJMra020021. View

van den Anker J, Schwab M, Kearns G . Developmental pharmacokinetics. Handb Exp Pharmacol. 2011; 205:51-75. DOI: 10.1007/978-3-642-20195-0_2. View

Whirl-Carrillo M, McDonagh E, Hebert J, Gong L, Sangkuhl K, Thorn C . Pharmacogenomics knowledge for personalized medicine. Clin Pharmacol Ther. 2012; 92(4):414-7. PMC: 3660037. DOI: 10.1038/clpt.2012.96. View

Weinshilboum R, Wang L . Pharmacogenomics: bench to bedside. Nat Rev Drug Discov. 2004; 3(9):739-48. DOI: 10.1038/nrd1497. View

Scott S, Sangkuhl K, Stein C, Hulot J, Mega J, Roden D . Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update. Clin Pharmacol Ther. 2013; 94(3):317-23. PMC: 3748366. DOI: 10.1038/clpt.2013.105. View

Relling M, Evans W . Pharmacogenomics in the clinic. Nature. 2015; 526(7573):343-50. PMC: 4711261. DOI: 10.1038/nature15817. View

Black 3rd J, Walker D, OKane D, Harmandayan M . Frequency of undetected CYP2D6 hybrid genes in clinical samples: impact on phenotype prediction. Drug Metab Dispos. 2011; 40(1):111-9. PMC: 3250050. DOI: 10.1124/dmd.111.040832. View

10.

Cook D, Sorensen K, Nishimura R, Ommen S, Lloyd F . A comprehensive information technology system to support physician learning at the point of care. Acad Med. 2014; 90(1):33-9. DOI: 10.1097/ACM.0000000000000551. View

11.

Retterer K, Juusola J, Cho M, Vitazka P, Millan F, Gibellini F . Clinical application of whole-exome sequencing across clinical indications. Genet Med. 2015; 18(7):696-704. DOI: 10.1038/gim.2015.148. View

12.

Zhu X, Petrovski S, Xie P, Ruzzo E, Lu Y, McSweeney K . Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios. Genet Med. 2015; 17(10):774-81. PMC: 4791490. DOI: 10.1038/gim.2014.191. View

13.

Manzi S, Fusaro V, Chadwick L, Brownstein C, Clinton C, Mandl K . Creating a scalable clinical pharmacogenomics service with automated interpretation and medical record result integration - experience from a pediatric tertiary care facility. J Am Med Inform Assoc. 2016; 24(1):74-80. PMC: 7654081. DOI: 10.1093/jamia/ocw052. View

14.

Ghanayem B, Bell D, Zhang Z, Kaminsky L, Shenfield G, Miners J . The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics. 1996; 6(4):341-9. DOI: 10.1097/00008571-199608000-00007. View

15.

Lazaridis K, Schahl K, Cousin M, Babovic-Vuksanovic D, Riegert-Johnson D, Gavrilova R . Outcome of Whole Exome Sequencing for Diagnostic Odyssey Cases of an Individualized Medicine Clinic: The Mayo Clinic Experience. Mayo Clin Proc. 2016; 91(3):297-307. DOI: 10.1016/j.mayocp.2015.12.018. View

16.

Arwood M, Chumnumwat S, Cavallari L, Nutescu E, Duarte J . Implementing Pharmacogenomics at Your Institution: Establishment and Overcoming Implementation Challenges. Clin Transl Sci. 2016; 9(5):233-245. PMC: 5121089. DOI: 10.1111/cts.12404. View

17.

Leeder J, Brown J, Soden S . Individualizing the use of medications in children: making Goldilocks happy. Clin Pharmacol Ther. 2014; 96(3):304-6. DOI: 10.1038/clpt.2014.130. View

18.

St Sauver J, Bielinski S, Olson J, Bell E, Mc Gree M, Jacobson D . Integrating Pharmacogenomics into Clinical Practice: Promise vs Reality. Am J Med. 2016; 129(10):1093-1099.e1. PMC: 5600492. DOI: 10.1016/j.amjmed.2016.04.009. View

19.

Neville K, Becker M, Goldman J, Kearns G . Developmental pharmacogenomics. Paediatr Anaesth. 2011; 21(3):255-65. DOI: 10.1111/j.1460-9592.2011.03533.x. View

20.

Yang Y, Muzny D, Xia F, Niu Z, Person R, Ding Y . Molecular findings among patients referred for clinical whole-exome sequencing. JAMA. 2014; 312(18):1870-9. PMC: 4326249. DOI: 10.1001/jama.2014.14601. View