Dataset Information

Randomized prospective evaluation of genome sequencing versus standard-of-care as a first molecular diagnostic test.

ABSTRACT:

Purpose

To evaluate the diagnostic yield and clinical relevance of clinical genome sequencing (cGS) as a first genetic test for patients with suspected monogenic disorders.

Methods

We conducted a prospective randomized study with pediatric and adult patients recruited from genetics clinics at Massachusetts General Hospital who were undergoing planned genetic testing. Participants were randomized into two groups: standard-of-care genetic testing (SOC) only or SOC and cGS.

Results

Two hundred four participants were enrolled, 202 were randomized to one of the intervention arms, and 99 received cGS. In total, cGS returned 16 molecular diagnoses that fully or partially explained the indication for testing in 16 individuals (16.2% of the cohort, 95% confidence interval [CI] 8.9-23.4%), which was not significantly different from SOC (18.2%, 95% CI 10.6-25.8%, P = 0.71). An additional eight molecular diagnoses reported by cGS had uncertain relevance to the participant's phenotype. Nevertheless, referring providers considered 20/24 total cGS molecular diagnoses (83%) to be explanatory for clinical features or worthy of additional workup.

Conclusion

cGS is technically suitable as a first genetic test. In our cohort, diagnostic yield was not significantly different from SOC. Further studies addressing other variant types and implementation challenges are needed to support feasibility and utility of broad-scale cGS adoption.

SUBMITTER: Brockman DG

PROVIDER: S-EPMC8488861 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

Randomized prospective evaluation of genome sequencing versus standard-of-care as a first molecular diagnostic test.

Brockman Deanna G DG Austin-Tse Christina A CA Pelletier Renée C RC Harley Caroline C Patterson Candace C Head Holly H Leonard Courtney Elizabeth CE O'Brien Kimberly K Mahanta Lisa M LM Lebo Matthew S MS Lu Christine Y CY Natarajan Pradeep P Khera Amit V AV Aragam Krishna G KG Kathiresan Sekar S Rehm Heidi L HL Udler Miriam S MS

Genetics in medicine : official journal of the American College of Medical Genetics 20210511 9

<h4>Purpose</h4>To evaluate the diagnostic yield and clinical relevance of clinical genome sequencing (cGS) as a first genetic test for patients with suspected monogenic disorders.<h4>Methods</h4>We conducted a prospective randomized study with pediatric and adult patients recruited from genetics clinics at Massachusetts General Hospital who were undergoing planned genetic testing. Participants were randomized into two groups: standard-of-care genetic testing (SOC) only or SOC and cGS.<h4>Result ...[more]

PMID: 33976420

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Dataset Information

Randomized prospective evaluation of genome sequencing versus standard-of-care as a first molecular diagnostic test.

Purpose

Methods

Results

Conclusion

Publications

Randomized prospective evaluation of genome sequencing versus standard-of-care as a first molecular diagnostic test.

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