{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T23:18:15Z","timestamp":1768346295981,"version":"3.49.0"},"reference-count":41,"publisher":"Portland Press Ltd.","issue":"16","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,8,15]]},"abstract":"<jats:p>Loss-of-function mutations of the the ATP-binding cassette-1 (ABCA1) gene are the cause of Tangier disease (TD) in homozygous subjects and familial HDL deficiency (FHD) in heterozygous subjects. These disorders are characterized by reduced plasma HDL-cholesterol (HDL-C) and altered efflux of cholesterol from cells. Previous studies in TD patients and ABCA1\u2212\/\u2212 murine models reported defects in platelet count, morphology, and function, but the issue is still controversial. We analyzed three subjects with low to very low HDL-C levels due to the loss-of-function mutations of the ABCA1 gene. Two related patients with FHD were heterozygous carriers of two mutations on the same ABCA1 allele; one, with TD, was homozygous for a different mutation. Mild to moderate thrombocytopenia was observed in all the patients. No morphological platelet abnormalities were detected under optical or EM. History of moderate bleeding tendency was recorded only in one of the FHD patients. Only limited alterations in platelet aggregation and activation of the integrin \u03b1IIb\u03b23 were observed in one FHD patient. While \u03b1-granule secretion (P-selectin), content, and secretion of platelet \u03b4-granules (serotonin, ATP, and ADP) and thromboxane (TX) A2 synthesis were normal in all the patients, the expression of lysosomal CD63, in response to some agonists, was reduced in TD patients. In conclusion, three patients carrying ABCA1 genetic variants had low platelet count, with the lowest values observed in TD, not associated with major alterations in platelet morphology and response to agonists or bleeding.<\/jats:p>","DOI":"10.1042\/cs20170195","type":"journal-article","created":{"date-parts":[[2017,6,21]],"date-time":"2017-06-21T00:10:48Z","timestamp":1498003848000},"page":"2095-2107","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Reduced platelet count, but no major platelet function abnormalities, are associated with loss-of-function ATP-binding cassette-1 gene mutations"],"prefix":"10.1042","volume":"131","author":[{"given":"Pietro","family":"Minuz","sequence":"first","affiliation":[{"name":"Department of Medicine, Section of Internal Medicine, University Laboratory for Medical Research (LURM) and Regional Centre for the Study of Platelets, University of Verona, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Meneguzzi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Internal Medicine, University Laboratory for Medical Research (LURM) and Regional Centre for the Study of Platelets, University of Verona, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eti\u00a0Alessandra","family":"Femia","sequence":"additional","affiliation":[{"name":"Unit\u00e0 di Medicina III, ASST Santi Paolo e Carlo and Dipartimento di Scienze della Salute, Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiano","family":"Fava","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Internal Medicine, University Laboratory for Medical Research (LURM) and Regional Centre for the Study of Platelets, University of Verona, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Calabria","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Internal Medicine, University Laboratory for Medical Research (LURM) and Regional Centre for the Study of Platelets, University of Verona, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariangela","family":"Scavone","sequence":"additional","affiliation":[{"name":"Unit\u00e0 di Medicina III, ASST Santi Paolo e Carlo and Dipartimento di Scienze della Salute, Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donatella","family":"Benati","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze, Biomedicina e Movimento, Sezione di Anatomia e Istologia, Universit\u00e0 di Verona, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Poli","sequence":"additional","affiliation":[{"name":"Section of Clinical Biochemistry, University of Verona, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Zancanaro","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze, Biomedicina e Movimento, Sezione di Anatomia e Istologia, Universit\u00e0 di Verona, Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastiano","family":"Calandra","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiziano","family":"Lucchi","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Clinic, Geriatric Operating Unit; Department of Internal Medicine and Medical Specialities, IRCCS Ca\u2019 Granda, Milano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"Unit\u00e0 di Medicina III, ASST Santi Paolo e Carlo and Dipartimento di Scienze della Salute, Universit\u00e0 degli Studi di Milano, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2017,7,24]]},"reference":[{"key":"2021113010511605800_B1","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/11905","article-title":"Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency","volume":"22","author":"Brooks-Wilson","year":"1999","journal-title":"Nat. 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