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Clinical impact of re-evaluating genes and variants implicated in dilated cardiomyopathy

Clinical impact of re-evaluating genes and variants implicated in dilated cardiomyopathy

Authors :
Stroeks, S.
Hellebrekers, D.
Claes, G.R.
Tayal, U.
Krapels, I.P.C.
Vanhoutte, E.K.
Wijngaard, A. van den
Henkens, M.
Ware, J.S.
Heymans, S.R.B.
Brunner, H.G.
Verdonschot, J.A.J.
Stroeks, S.
Hellebrekers, D.
Claes, G.R.
Tayal, U.
Krapels, I.P.C.
Vanhoutte, E.K.
Wijngaard, A. van den
Henkens, M.
Ware, J.S.
Heymans, S.R.B.
Brunner, H.G.
Verdonschot, J.A.J.
Source :
Genetics in Medicine; 2186; 2193; 1098-3600; 11; 23; ~Genetics in Medicine~2186~2193~~~1098-3600~11~23~~
Publication Year :
2021

Abstract

Contains fulltext : 243935.pdf (Publisher’s version ) (Open Access)<br />PURPOSE: Accurate interpretation of variants detected in dilated cardiomyopathy (DCM) is crucial for patient care but has proven challenging. We applied a set of proposed refined American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria for DCM, reclassified all detected variants in robust genes, and associated these results to patients' phenotype. METHODS: The study included 902 DCM probands from the Maastricht Cardiomyopathy Registry who underwent genetic testing. Two gene panel sizes (extended n = 48; and robust panel n = 14) and two standards of variant classification (standard versus the proposed refined ACMG/AMP criteria) were applied to compare genetic yield. RESULTS: A pathogenic or likely pathogenic (P/LP) variant was found in 17.8% of patients, and a variant of uncertain significance (VUS) was found in 32.8% of patients when using method 1 (extended panel (n = 48) + standard ACMG/AMP), compared to respectively 16.9% and 12.9% when using method 2 (robust panel (n = 14) + standard ACMG/AMP), and respectively 14% and 14.5% using method 3 (robust panel (n = 14) + refined ACMG/AMP). Patients with P/LP variants had significantly lower event-free survival compared to genotype-negative DCM patients. CONCLUSION: Stringent gene selection for DCM genetic testing reduced the number of VUS while retaining ability to detect similar P/LP variants. The number of genes on diagnostic panels should be limited to genes that have the highest signal to noise ratio.

Details

Database :
OAIster
Journal :
Genetics in Medicine; 2186; 2193; 1098-3600; 11; 23; ~Genetics in Medicine~2186~2193~~~1098-3600~11~23~~
Publication Type :
Electronic Resource
Accession number :
edsoai.on1377068509
Document Type :
Electronic Resource