Limits...
Actionable clinical decisions based on comprehensive genomic evaluation in asymptomatic adults.

Pillar N, Isakov O, Weissglas-Volkov D, Botchan S, Friedman E, Arber N, Shomron N - Mol Genet Genomic Med (2015)

Bottom Line: Herein, we aim to examine whether WES is useful in screening asymptomatic individuals for actionable interventions, which has not yet been established.Furthermore, more than 80% of the participants (21) carried 1-3 genetic variants with an associated clinical guideline for an altered drug dosing or administration based on the FDA's table of pharmacogenomics.These results support WES potential not only to answer specific diagnostic questions presented by the relevant personal and/or family history but also to uncover clinically important genetic findings unrelated to the primary indication for sequencing.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine, Tel Aviv University Tel Aviv, 69978, Israel.

ABSTRACT
Whole-exome sequencing (WES) arises as a new approach in diagnosing individuals affected by multigenic and complex phenotypes. Herein, we aim to examine whether WES is useful in screening asymptomatic individuals for actionable interventions, which has not yet been established. Twenty-five healthy adults underwent WES, bioinformatics, and manual curation of their exomes. Six participants (24%) harbored significant, management-changing variants in cancer predisposition genes, American College of Medical Genetics, and genomics reportable cardiac diseases and pharmacogenomic biomarkers that have led to clinical recommendations and interventions. Furthermore, more than 80% of the participants (21) carried 1-3 genetic variants with an associated clinical guideline for an altered drug dosing or administration based on the FDA's table of pharmacogenomics. These results support WES potential not only to answer specific diagnostic questions presented by the relevant personal and/or family history but also to uncover clinically important genetic findings unrelated to the primary indication for sequencing.

No MeSH data available.


Related in: MedlinePlus

Deleterious variants in pharmacogenomics, cardiovascular, and cancer genes. (A) Pharmacogenomics-related genes (B) Cardiovascular-related genes (C) Cancer-related genes. The bracketed numbers represent number of individuals with computationally predicted deleterious variants in each gene.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4585451&req=5

fig01: Deleterious variants in pharmacogenomics, cardiovascular, and cancer genes. (A) Pharmacogenomics-related genes (B) Cardiovascular-related genes (C) Cancer-related genes. The bracketed numbers represent number of individuals with computationally predicted deleterious variants in each gene.

Mentions: Six patients (24%) harbored deleterious variants in CVS disorders-related genes. Thoracic aortic aneurysms-related variants were detected in five patients (20%) and one patient (5%) had hypertrophic cardiomyopathy-related variant. Variants predicted to be deleterious in cancer, cardiovascular, and pharmacogenomics genes are presented in Figure1.


Actionable clinical decisions based on comprehensive genomic evaluation in asymptomatic adults.

Pillar N, Isakov O, Weissglas-Volkov D, Botchan S, Friedman E, Arber N, Shomron N - Mol Genet Genomic Med (2015)

Deleterious variants in pharmacogenomics, cardiovascular, and cancer genes. (A) Pharmacogenomics-related genes (B) Cardiovascular-related genes (C) Cancer-related genes. The bracketed numbers represent number of individuals with computationally predicted deleterious variants in each gene.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585451&req=5

fig01: Deleterious variants in pharmacogenomics, cardiovascular, and cancer genes. (A) Pharmacogenomics-related genes (B) Cardiovascular-related genes (C) Cancer-related genes. The bracketed numbers represent number of individuals with computationally predicted deleterious variants in each gene.
Mentions: Six patients (24%) harbored deleterious variants in CVS disorders-related genes. Thoracic aortic aneurysms-related variants were detected in five patients (20%) and one patient (5%) had hypertrophic cardiomyopathy-related variant. Variants predicted to be deleterious in cancer, cardiovascular, and pharmacogenomics genes are presented in Figure1.

Bottom Line: Herein, we aim to examine whether WES is useful in screening asymptomatic individuals for actionable interventions, which has not yet been established.Furthermore, more than 80% of the participants (21) carried 1-3 genetic variants with an associated clinical guideline for an altered drug dosing or administration based on the FDA's table of pharmacogenomics.These results support WES potential not only to answer specific diagnostic questions presented by the relevant personal and/or family history but also to uncover clinically important genetic findings unrelated to the primary indication for sequencing.

View Article: PubMed Central - PubMed

Affiliation: Faculty of Medicine, Tel Aviv University Tel Aviv, 69978, Israel.

ABSTRACT
Whole-exome sequencing (WES) arises as a new approach in diagnosing individuals affected by multigenic and complex phenotypes. Herein, we aim to examine whether WES is useful in screening asymptomatic individuals for actionable interventions, which has not yet been established. Twenty-five healthy adults underwent WES, bioinformatics, and manual curation of their exomes. Six participants (24%) harbored significant, management-changing variants in cancer predisposition genes, American College of Medical Genetics, and genomics reportable cardiac diseases and pharmacogenomic biomarkers that have led to clinical recommendations and interventions. Furthermore, more than 80% of the participants (21) carried 1-3 genetic variants with an associated clinical guideline for an altered drug dosing or administration based on the FDA's table of pharmacogenomics. These results support WES potential not only to answer specific diagnostic questions presented by the relevant personal and/or family history but also to uncover clinically important genetic findings unrelated to the primary indication for sequencing.

No MeSH data available.


Related in: MedlinePlus