{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:27:31Z","timestamp":1777444051342,"version":"3.51.4"},"reference-count":40,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2016,9,28]],"date-time":"2016-09-28T00:00:00Z","timestamp":1475020800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Biochem"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Detection of disease-associated mutations in patients with familial hypercholesterolaemia is crucial for early interventions to reduce risk of cardiovascular disease. Screening for these mutations represents a methodological challenge since more than 1200 different causal mutations in the low-density lipoprotein receptor has been identified. A number of methodological approaches have been developed for screening by clinical diagnostic laboratories.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using primers targeting, the low-density lipoprotein receptor, apolipoprotein B, and proprotein convertase subtilisin\/kexin type 9, we developed a novel Ion Torrent-based targeted re-sequencing method. We validated this in a West Midlands-UK small cohort of 58 patients screened in parallel with other mutation-targeting methods, such as multiplex polymerase chain reaction (Elucigene FH20), oligonucleotide arrays (Randox familial hypercholesterolaemia array) or the Illumina next-generation sequencing platform.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this small cohort, the next-generation sequencing method achieved excellent analytical performance characteristics and showed 100% and 89% concordance with the Randox array and the Elucigene FH20 assay. Investigation of the discrepant results identified two cases of mutation misclassification of the Elucigene FH20 multiplex polymerase chain reaction assay. A number of novel mutations not previously reported were also identified by the next-generation sequencing method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Ion Torrent-based next-generation sequencing can deliver a suitable alternative for the molecular investigation of familial hypercholesterolaemia patients, especially when comprehensive mutation screening for rare or unknown mutations is required.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0004563216629170","type":"journal-article","created":{"date-parts":[[2016,1,9]],"date-time":"2016-01-09T20:07:44Z","timestamp":1452370064000},"page":"654-662","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Molecular testing for familial hypercholesterolaemia-associated mutations in a UK-based cohort: development of an NGS-based method and comparison with multiplex polymerase chain reaction and oligonucleotide arrays"],"prefix":"10.1177","volume":"53","author":[{"given":"Anne","family":"Reiman","sequence":"first","affiliation":[{"name":"Division of Translational and Systems Medicine, Warwick Medical School, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarojini","family":"Pandey","sequence":"additional","affiliation":[{"name":"Pathology Service, University Hospital Coventry and Warwickshire, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kate L","family":"Lloyd","sequence":"additional","affiliation":[{"name":"Systems Biology, University of Warwick, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel","family":"Dyer","sequence":"additional","affiliation":[{"name":"Systems Biology, University of Warwick, 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