{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T01:37:56Z","timestamp":1792201076007,"version":"4.4.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Genomic and Precision Medicine"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>\n              Sitosterolemia is a rare autosomal recessive disorder caused by homozygous or compound heterozygous variants in\n              <jats:italic>ABCG5\/ABCG8<\/jats:italic>\n              . The disease is characterized by increased plasma plant sterols. Small case series suggest that patients with sitosterolemia have wide phenotypic heterogeneity with great variability on either plasma cholesterol levels or development of atherosclerotic cardiovascular disease. The present study aims to characterize the prevalence and clinical features of sitosterolemia participating in a familial hypercholesterolemia genetic cascade screening program.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              From 443 familial hypercholesterolemia index cases, 260 were negative for familial hypercholesterolemia genes and were sequenced for the\n              <jats:italic>ABCG5\/8<\/jats:italic>\n              genes. Clinical and laboratory characteristics of affected individuals were determined.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Eight (3.1%) index cases were found to be homozygous or compound heterozygous variant for\n              <jats:italic>ABCG5\/ABCG8<\/jats:italic>\n              genes, confirming the genetic diagnosis of sitosterolemia. Screening their relatives led to the identification of 6 additional confirmed sitosterolemia cases (3 homozygous and 3 compound heterozygous variant) and 18 carriers (heterozygous). The mean age of identified sitosterolemia cases (n=14) was 37.2\u00b119.8 years, 50% were females, and 78.6% (all adults) presented either clinical or subclinical atherosclerotic cardiovascular disease. As expected, affected individuals presented elevated plasma plant sterol levels (mean \u03b2-Sitosterol and campesterol, respectively, 160.3\u00b1107.1 and 32.0\u00b119.6 \u00b5g\/mL) and the highest plasma LDL (low-density lipoprotein)-cholesterol was 269.0\u00b1120.0 mg\/dL (range: 122\u2013521 mg\/dL). LDL-cholesterol mean reduction with therapy among cases was 65%. Eighty-three percent (83%) of identified sitosterolemia patients presented hematologic abnormalities.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Testing genes associated with sitosterolemia in the molecular routine workflow of a familial hypercholesterolemia cascade screening program allowed the precise diagnosis of sitosterolemia in a substantial number of patients with varying LDL-C levels and high incidence of early atherosclerotic cardiovascular disease and hematologic abnormalities.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgen.121.003390","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T13:49:28Z","timestamp":1652363368000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":31,"title":["Screening of\n            <i>ABCG5<\/i>\n            and\n            <i>ABCG8<\/i>\n            Genes for Sitosterolemia in a Familial Hypercholesterolemia Cascade Screening Program"],"prefix":"10.1161","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8729-4440","authenticated-orcid":true,"given":"Mauricio Teruo","family":"Tada","sequence":"first","affiliation":[{"name":"Laboratory of Genetics and Molecular Cardiology (LIM13) (M.T.T., I.R.L., T.G.M.O., C.E.J., J.E.K., A.C.P.), University of S\u00e3o Paulo Medical School Hospital."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4157-664X","authenticated-orcid":true,"given":"Viviane Zorzanelli","family":"Rocha","sequence":"additional","affiliation":[{"name":"Lipid Clinic, Heart Institute (InCor) (V.Z.R., A.P.C., M.H.M., R.D.S.), University of S\u00e3o Paulo Medical School Hospital."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella Ramos","family":"Lima","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Cardiology (LIM13) (M.T.T., I.R.L., T.G.M.O., C.E.J., J.E.K., A.C.P.), University of S\u00e3o Paulo Medical School Hospital."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Th\u00e9o Gremen Mimary","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Cardiology (LIM13) (M.T.T., I.R.L., T.G.M.O., C.E.J., J.E.K., A.C.P.), University of S\u00e3o Paulo Medical School Hospital."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2881-1820","authenticated-orcid":true,"given":"Ana Paula","family":"Chacra","sequence":"additional","affiliation":[{"name":"Lipid Clinic, Heart Institute (InCor) (V.Z.R., A.P.C., M.H.M., R.D.S.), University of S\u00e3o Paulo Medical School Hospital."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4487-5701","authenticated-orcid":true,"given":"Marcio Hiroshi","family":"Miname","sequence":"additional","affiliation":[{"name":"Lipid Clinic, Heart Institute (InCor) (V.Z.R., A.P.C., M.H.M., R.D.S.), University of S\u00e3o Paulo Medical School Hospital."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6769-5412","authenticated-orcid":true,"given":"Val\u00e9ria Sutti","family":"Nunes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de L\u00edpides (LIM10), Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo (HCFMUSP), S\u00e3o Paulo (V.S.N., E.R.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna Regina","family":"Nakandakare","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de L\u00edpides (LIM10), Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo (HCFMUSP), S\u00e3o Paulo (V.S.N., E.R.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3816-5612","authenticated-orcid":true,"given":"Maria Helane","family":"Costa Gurgel Castelo","sequence":"additional","affiliation":[{"name":"Medical School, Federal University of Cear\u00e1, Fortaleza (M.H.C.G.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinthia Elim","family":"Jannes","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Cardiology (LIM13) (M.T.T., I.R.L., T.G.M.O., C.E.J., J.E.K., A.C.P.), University of S\u00e3o Paulo Medical School Hospital."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9860-6582","authenticated-orcid":true,"given":"Raul D.","family":"Santos","sequence":"additional","affiliation":[{"name":"Lipid Clinic, Heart Institute (InCor) (V.Z.R., A.P.C., M.H.M., R.D.S.), University of S\u00e3o Paulo Medical School Hospital."},{"name":"Academic Research Organization, Hospital Israelita Albert Einstein, S\u00e3o Paulo, Brazil (R.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5464-1792","authenticated-orcid":true,"given":"Jos\u00e9 Eduardo","family":"Krieger","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Cardiology (LIM13) (M.T.T., I.R.L., T.G.M.O., C.E.J., J.E.K., A.C.P.), University of S\u00e3o Paulo Medical School Hospital."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7782-5540","authenticated-orcid":true,"given":"Alexandre Costa","family":"Pereira","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Molecular Cardiology (LIM13) (M.T.T., I.R.L., T.G.M.O., C.E.J., J.E.K., A.C.P.), University of S\u00e3o Paulo Medical School Hospital."},{"name":"Genetics Department, Harvard Medical School, Boston, MA (A.C.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2017.05.002"},{"key":"e_1_3_3_3_2","article-title":"Sitosterolemia.","author":"Myrie S","year":"2013","unstructured":"Myrie, SB, Steiner, RD, Mymin D. Sitosterolemia. 2013 Apr 4 [Updated 2020 Jul 16]. In: Adam, MP, Ardinger, HH, Pagon, RA, et al., eds. GeneReviews\u00ae [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2021. Available from: https:\/\/rarediseases.org\/rare-diseases\/sitosterolemia\/","journal-title":"GeneReviews\u00ae [Internet]"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI107640"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20190130"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGEN.119.002871"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-014-0424-2"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5497.1771"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R017855"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)41411-7"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.6065\/apem.2016.21.1.7"},{"key":"e_1_3_3_12_2","volume-title":"GeneReviews\u00ae [Internet]","author":"Merkens LS","year":"2013","unstructured":"Merkens, LS, Myrie, SB, Steiner, RD, et al. Sitosterolemia. 2013 Apr 4 [Updated 2018 May 17]. In: Adam, MP, Ardinger, HH, Pagon, RA, et al., editors. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Accessed May 12, 2022. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2014.02.030"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000015013"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2019.02.003"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22040589"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.5551\/jat.RV17024"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2017.10.013"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2015.09.011"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.05.044"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2017.06.917"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht273"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M606339200"},{"key":"e_1_3_3_25_2","first-page":"1","article-title":"ABCG5 and ABCG8 gene variations associated with sitosterolemia and platelet dysfunction platelet dysfunction.","volume":"00","author":"Bastida JM","year":"2020","unstructured":"Bastida, JM, Benito, R, Gonz\u00e1lez-porras, JR, Rivera, J, Bastida, JM. ABCG5 and ABCG8 gene variations associated with sitosterolemia and platelet dysfunction platelet dysfunction. Platelets. 2020;00:1\u20135. 10.1080\/09537104.2020.1779926","journal-title":"Platelets"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2017.72"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-019-1183-4"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1177\/1074248418780733"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v8.i22.924"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1159\/000170146"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.med.0000432611.03732.49"},{"key":"e_1_3_3_32_2","unstructured":"U.S. Department of Health and Human Services Health Resources and Services Administration Guide for HIV\/AIDS Clinical Care - 2014 Edition. Rockville MD: U.S. Department of Health and Human Services 2014. Accessed May 12 2022. Available from: https:\/\/hab.hrsa.gov\/sites\/default\/files\/hab\/clinical-quality-management\/2014guide.pdf"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22981"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2010.09.039"}],"container-title":["Circulation: Genomic and Precision Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCGEN.121.003390","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T01:25:39Z","timestamp":1715563539000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCGEN.121.003390"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["10.1161\/CIRCGEN.121.003390"],"URL":"https:\/\/doi.org\/10.1161\/circgen.121.003390","relation":{},"ISSN":["2574-8300"],"issn-type":[{"value":"2574-8300","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6]]},"assertion":[{"value":"2021-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-03-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}