Amanda J Hooper1,2, John R Burnett1,2,3, Damon A Bell1,2,3, Gerald F Watts4,5. 1. Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital & Fiona Stanley Hospital Network, Perth, Australia. 2. School of Medicine, Royal Perth Hospital, University of Western Australia, GPO Box X2213, Perth, WA, 6847, Australia. 3. Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, Australia. 4. School of Medicine, Royal Perth Hospital, University of Western Australia, GPO Box X2213, Perth, WA, 6847, Australia. gerald.watts@uwa.edu.au. 5. Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, Australia. gerald.watts@uwa.edu.au.
Abstract
PURPOSE OF REVIEW: We summarize recent advances in the understanding of genetic testing in familial hypercholesterolemia (FH), the use of expanded FH next-generation sequencing panels, and directions for future research. RECENT FINDINGS: The uptake of massively parallel sequencing in research and diagnostic laboratories has enabled expanded testing for FH and its phenocopies, with the added advantage that copy number variants can be detected. However, increasing the number of genes tested increases the number of variants detected, which may or may not be pathogenic. Guidelines for assessing variant pathogenicity will assist the provision of accurate and consistent interpretations between centers. Expanded FH panels can identify mutations in other relevant genes, such as APOE, LIPA, and ABCG5/8 and enable the identification of polygenic hypercholesterolemia using LDL genetic risk scores. Increased awareness and understanding of genomics by the public, patients, and health professionals is critical for effectively translating into practice new advances in genetic testing for FH.
PURPOSE OF REVIEW: We summarize recent advances in the understanding of genetic testing in familial hypercholesterolemia (FH), the use of expanded FH next-generation sequencing panels, and directions for future research. RECENT FINDINGS: The uptake of massively parallel sequencing in research and diagnostic laboratories has enabled expanded testing for FH and its phenocopies, with the added advantage that copy number variants can be detected. However, increasing the number of genes tested increases the number of variants detected, which may or may not be pathogenic. Guidelines for assessing variant pathogenicity will assist the provision of accurate and consistent interpretations between centers. Expanded FH panels can identify mutations in other relevant genes, such as APOE, LIPA, and ABCG5/8 and enable the identification of polygenic hypercholesterolemia using LDL genetic risk scores. Increased awareness and understanding of genomics by the public, patients, and health professionals is critical for effectively translating into practice new advances in genetic testing for FH.
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Authors: Ari E Horton; Andrew C Martin; Shubha Srinivasan; Robert N Justo; Nicola K Poplawski; David Sullivan; Tom Brett; Clara K Chow; Stephen J Nicholls; Jing Pang; Gerald F Watts Journal: J Paediatr Child Health Date: 2022-07-15 Impact factor: 1.929
Authors: Gerald F Watts; David R Sullivan; David L Hare; Karam M Kostner; Ari E Horton; Damon A Bell; Tom Brett; Ronald J Trent; Nicola K Poplawski; Andrew C Martin; Shubha Srinivasan; Robert N Justo; Clara K Chow; Jing Pang Journal: Am J Prev Cardiol Date: 2021-02-04