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Review Article

Sitosterolemia：诊断，代谢和血液异常，心血管疾病和管理

卷 26, 期 37, 2019

页: [6766 - 6775] 页: 10

弟呕挨: 10.2174/0929867325666180705145900

价格: $65

摘要

谷固醇血症是一种不明患病的隐性遗传性代谢疾病，其特征在于血浆植物固醇水平升高。它分别由ABCG5和ABCG8基因中的28和31个变体引起，其特征是易吸收血浆中植物甾醇的毒性水平并易于累积。其临床表现极为不同。主要临床特征是肌腱和皮肤黄瘤，关节炎或关节痛，过早的心血管疾病和动脉粥样硬化。这些特征与家族性高胆固醇血症（FH）共同存在，使得谷固醇血症有可能被误诊为纯合子FH，尤其是在小儿患者中。在这种情况下，特定的基于色谱的实验室方法对于区分谷固醇和胆固醇至关重要。血液学异常（溶血性贫血和大血小板减少症）可能出现在25-35％的患者中，其中通常与主要临床特征相关，如70％的病例。在这种情况下，外周血涂片是必不可少的，并显示出巨大的血小板和口腔细胞。 ABCG5 / ABCG8中只有21个致病性变异与大血小板减少症相关。大多数医生仍然不认识这些血液学异常或将它们与谷固醇血症相关联。患者可能会长期遭受免疫性血小板减少症的误诊，极有可能接受有害疗法或无法从低胆固醇饮食和/或依泽替米贝的黄金标准治疗中受益。该药物可降低血浆植物固醇的水平，引起黄瘤退化，并可减轻血液学异常。最后，为了鉴定遗传缺陷，高通量测序的最新进展，特别是在使用预先指定的基因的靶向测序方面，已被纳入遗传疾病领域的一线研究方法。

关键词: 血小板疾病，谷固醇，大血小板减少症，高通量核苷酸测序，基因检测，高胆固醇血症。

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[1]
Bhattacharyya, A.K.; Connor, W.E. Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters. J. Clin. Invest., 1974, 53(4), 1033-1043.
[http://dx.doi.org/10.1172/JCI107640] [PMID: 4360855]
[2]
Patel, S.B.; Salen, G.; Hidaka, H.; Kwiterovich, P.O.; Stalenhoef, A.F.; Miettinen, T.A.; Grundy, S.M.; Lee, M.H.; Rubenstein, J.S.; Polymeropoulos, M.H.; Brownstein, M.J. Mapping a gene involved in regulating dietary cholesterol absorption. The sitosterolemia locus is found at chromosome 2p21. J. Clin. Invest., 1998, 102(5), 1041-1044.
[http://dx.doi.org/10.1172/JCI3963] [PMID: 9727073]
[3]
Berge, K.E.; Tian, H.; Graf, G.A.; Yu, L.; Grishin, N.V.; Schultz, J.; Kwiterovich, P.; Shan, B.; Barnes, R.; Hobbs, H.H. Accumulation of dietary cholesterol in sitosterolemia caused by mutations in adjacent ABC transporters. Science, 2000, 290(5497), 1771-1775.
[http://dx.doi.org/10.1126/science.290.5497.1771] [PMID: 11099417]
[4]
Lee, M.H.; Lu, K.; Hazard, S.; Yu, H.; Shulenin, S.; Hidaka, H.; Kojima, H.; Allikmets, R.; Sakuma, N.; Pegoraro, R.; Srivastava, A.K.; Salen, G.; Dean, M.; Patel, S.B. Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nat. Genet., 2001, 27(1), 79-83.
[http://dx.doi.org/10.1038/83799] [PMID: 11138003]
[5]
Hubacek, J.A.; Berge, K.E.; Cohen, J.C.; Hobbs, H.H. Mutations in ATP-cassette binding proteins G5 (ABCG5) and G8 (ABCG8) causing sitosterolemia. Hum. Mutat., 2001, 18(4), 359-360.
[http://dx.doi.org/10.1002/humu.1206] [PMID: 11668628]
[6]
Kidambi, S.; Patel, S.B. Sitosterolaemia: pathophysiology, clinical presentation and laboratory diagnosis. J. Clin. Pathol., 2008, 61(5), 588-594.
[http://dx.doi.org/10.1136/jcp.2007.049775] [PMID: 18441155]
[7]
Lu, K.; Lee, M.H.; Hazard, S.; Brooks-Wilson, A.; Hidaka, H.; Kojima, H.; Ose, L.; Stalenhoef, A.F.; Mietinnen, T.; Bjorkhem, I.; Bruckert, E.; Pandya, A.; Brewer, H.B. Jr.; Salen, G.; Dean, M.; Srivastava, A.; Patel, S.B. Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively. Am. J. Hum. Genet., 2001, 69(2), 278-290.
[http://dx.doi.org/10.1086/321294] [PMID: 11452359]
[8]
Yoo, E.G. Sitosterolemia: a review and update of pathophysiology, clinical spectrum, diagnosis, and management. Ann. Pediatr. Endocrinol. Metab., 2016, 21(1), 7-14.
[http://dx.doi.org/10.6065/apem.2016.21.1.7] [PMID: 27104173]
[9]
Weingärtner, O.; Teupser, D.; Patel, S.B. The atherogenicity of plant sterols: the evidence from genetics to clinical trials. J. AOAC Int., 2015, 98(3), 742-749.
[http://dx.doi.org/10.5740/jaoacint.SGEWeingartner] [PMID: 25942705]
[10]
Escolà-Gil, J.C.; Quesada, H.; Julve, J.; Martín-Campos, J.M.; Cedó, L.; Blanco-Vaca, F. Sitosterolemia: diagnosis, investigation, and management. Curr. Atheroscler. Rep., 2014, 16(7), 424.
[http://dx.doi.org/10.1007/s11883-014-0424-2] [PMID: 24821603]
[11]
McDaniel, A.L.; Alger, H.M.; Sawyer, J.K.; Kelley, K.L.; Kock, N.D.; Brown, J.M.; Temel, R.E.; Rudel, L.L. Phytosterol feeding causes toxicity in ABCG5/G8 knockout mice. Am. J. Pathol., 2013, 182(4), 1131-1138.
[http://dx.doi.org/10.1016/j.ajpath.2012.12.014] [PMID: 23380580]
[12]
Tzavella, E.; Hatzimichael, E.; Kostara, C.; Bairaktari, E.; Elisaf, M.; Tsimihodimos, V. Sitosterolemia: A multifaceted metabolic disorder with important clinical consequences. J. Clin. Lipidol., 2017, 11(4), 1095-1100.
[http://dx.doi.org/10.1016/j.jacl.2017.04.116] [PMID: 28545928]
[13]
Rees, D.C.; Iolascon, A.; Carella, M.; O’marcaigh, A.S.; Kendra, J.R.; Jowitt, S.N.; Wales, J.K.; Vora, A.; Makris, M.; Manning, N.; Nicolaou, A.; Fisher, J.; Mann, A.; Machin, S.J.; Clayton, P.T.; Gasparini, P.; Stewart, G.W. Stomatocytic haemolysis and macrothrombocytopenia (Mediterranean stomatocytosis/macrothrombocytopenia) is the haematological presentation of phytosterolaemia. Br. J. Haematol., 2005, 130(2), 297-309.
[http://dx.doi.org/10.1111/j.1365-2141.2005.05599.x] [PMID: 16029460]
[14]
Ono, S.; Matsuda, J.; Saito, A.; Yamamoto, T.; Fujimoto, W.; Shimizu, H.; Dateki, S.; Ouchi, K. A case of sitosterolemia due to compound heterozygous mutations in ABCG5: clinical features and treatment outcomes obtained with colestimide and ezetimibe. Clin. Pediatr. Endocrinol., 2017, 26(1), 17-23.
[http://dx.doi.org/10.1297/cpe.26.17] [PMID: 28203044]
[15]
Renner, C.; Connor, W.E.; Steiner, R.D. Sitosterolemia presenting as pseudohomozygous familial hypercholesterolemia. Clin. Med. Res., 2016, 14(2), 103-108.
[http://dx.doi.org/10.3121/cmr.2016.1294] [PMID: 27231115]
[16]
Wang, G.; Cao, L.; Wang, Z.; Jiang, M.; Sun, X.; Bai, X.; Ruan, C. Macrothrombocytopenia/stomatocytosis specially associated with phytosterolemia. Clin. Appl. Thromb. Hemost., 2012, 18(6), 582-587.
[http://dx.doi.org/10.1177/1076029611435090] [PMID: 22297561]
[17]
Niu, D.M.; Chong, K.W.; Hsu, J.H.; Wu, T.J.; Yu, H.C.; Huang, C.H.; Lo, M.Y.; Kwok, C.F.; Kratz, L.E.; Ho, L.T. Clinical observations, molecular genetic analysis, and treatment of sitosterolemia in infants and children. J. Inherit. Metab. Dis., 2010, 33(4), 437-443.
[http://dx.doi.org/10.1007/s10545-010-9126-2] [PMID: 20521169]
[18]
Kamelska, A.M.; Pietrzak-Fiećko, R.; Bryl, K. Variation of the cholesterol content in breast milk during 10 days collection at early stages of lactation. Acta Biochim. Pol., 2012, 59(2), 243-247.
[http://dx.doi.org/10.18388/abp.2012_2145] [PMID: 22540113]
[19]
Buonuomo, P.S.; Iughetti, L.; Pisciotta, L.; Rabacchi, C.; Papadia, F.; Bruzzi, P.; Tummolo, A.; Bartuli, A.; Cortese, C.; Bertolini, S.; Calandra, S. Timely diagnosis of sitosterolemia by next generation sequencing in two children with severe hypercholesterolemia. Atherosclerosis, 2017, 262, 71-77.
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.05.002] [PMID: 28521186]
[20]
Wang, W.; Jiang, L.; Chen, P.P.; Wu, Y.; Su, P.Y.; Wang, L.Y. A case of sitosterolemia misdiagnosed as familial hypercholesterolemia: A 4-year follow-up. J. Clin. Lipidol., 2018, 12(1), 236-239.
[http://dx.doi.org/10.1016/j.jacl.2017.10.008] [PMID: 29246730]
[21]
Oosterveer, D.M.; Versmissen, J.; Yazdanpanah, M.; Hamza, T.H.; Sijbrands, E.J. Differences in characteristics and risk of cardiovascular disease in familial hypercholesterolemia patients with and without tendon xanthomas: a systematic review and meta-analysis. Atherosclerosis, 2009, 207(2), 311-317.
[http://dx.doi.org/10.1016/j.atherosclerosis.2009.04.009] [PMID: 19439299]
[22]
Menotti, A.; Puddu, P.E.; Lanti, M.; Maiani, G.; Fidanza, F. Cardiovascular risk factors predict survival in middle-aged men during 50 years. Eur. J. Intern. Med., 2013, 24(1), 67-74.
[http://dx.doi.org/10.1016/j.ejim.2012.08.004] [PMID: 22954458]
[23]
Wang, Z.; Cao, L.; Su, Y.; Wang, G.; Wang, R.; Yu, Z.; Bai, X.; Ruan, C. Specific macrothrombocytopenia/hemolytic anemia associated with sitosterolemia. Am. J. Hematol., 2014, 89(3), 320-324.
[http://dx.doi.org/10.1002/ajh.23619] [PMID: 24166850]
[24]
Stewart, G.W.; Lloyd, J.; Pegel, K. Mediterranean stomato-cytosis/macrothrombocytopenia: update from Adelaide, Australia. Br. J. Haematol., 2006, 132(5), 660-661.
[http://dx.doi.org/10.1111/j.1365-2141.2006.05973.x] [PMID: 16445847]
[25]
Wang, G.; Wang, Z.; Liang, J.; Cao, L.; Bai, X.; Ruan, C. A phytosterolemia patient presenting exclusively with macrothrombocytopenia and stomatocytic hemolysis. Acta Haematol., 2011, 126(2), 95-98.
[http://dx.doi.org/10.1159/000327248] [PMID: 21576934]
[26]
Neff, A.T. Sitosterolemia’s stomatocytosis and macrothrombocytopenia. Blood, 2012, 120(22), 4283.
[http://dx.doi.org/10.1182/blood-2012-06-429449] [PMID: 23310983]
[27]
Keller, S.; Prechtl, D.; Aslanidis, C.; Ceglarek, U.; Thiery, J.; Schmitz, G.; Jahreis, G. Increased plasma plant sterol concentrations and a heterozygous amino acid exchange in ATP binding cassette transporter ABCG5: a case report. Eur. J. Med. Genet., 2011, 54(4), e458-e460.
[http://dx.doi.org/10.1016/j.ejmg.2011.05.003] [PMID: 21664501]
[28]
Bastida, J.M.; Del Rey, M.; Revilla, N.; Benito, R.; Perez-Andrés, M.; González, B.; Riesco, S.; Janusz, K.; Padilla, J.; Hortal Benito-Sendin, A.; Bueno, D.; Blanco, E.; Hernández-Rivas, M.; Vicente, V.; Rivera, J.; González-Porras, R.; Lozano, M.L. Wiskott-Aldrich syndrome in a child presenting with macrothrombocytopenia. Platelets, 2017, 28(4), 417-420.
[http://dx.doi.org/10.1080/09537104.2016.1246715] [PMID: 27885891]
[29]
Balduini, C.L.; Savoia, A.; Seri, M. Inherited thrombocytopenias frequently diagnosed in adults. J. Thromb. Haemost., 2013, 11(6), 1006-1019.
[http://dx.doi.org/10.1111/jth.12196] [PMID: 23510089]
[30]
Bastida, J.M.; Benito, R.; Janusz, K.; Díez-Campelo, M.; Hernández-Sánchez, J.M.; Marcellini, S.; Girós, M.; Rivera, J.; Lozano, M.L.; Hortal, A.; Hernández-Rivas, J.M.; González-Porras, J.R. Two novel variants of the ABCG5 gene cause xanthelasmas and macrothrombocytopenia: a brief review of hematologic abnormalities of sitosterolemia. J. Thromb. Haemost., 2017, 15(9), 1859-1866.
[http://dx.doi.org/10.1111/jth.13777] [PMID: 28696550]
[31]
Kanaji, T.; Kanaji, S.; Montgomery, R.R.; Patel, S.B.; Newman, P.J. Platelet hyperreactivity explains the bleeding abnormality and macrothrombocytopenia in a murine model of sitosterolemia. Blood, 2013, 122(15), 2732-2742.
[http://dx.doi.org/10.1182/blood-2013-06-510461] [PMID: 23926302]
[32]
Chase, T.H.; Lyons, B.L.; Bronson, R.T.; Foreman, O.; Donahue, L.R.; Burzenski, L.M.; Gott, B.; Lane, P.; Harris, B.; Ceglarek, U.; Thiery, J.; Wittenburg, H.; Thon, J.N.; Italiano, J.E. Jr.; Johnson, K.R.; Shultz, L.D. The mouse mutation “thrombocytopenia and cardiomyopathy” (trac) disrupts Abcg5: a spontaneous single gene model for human hereditary phytosterolemia/sitosterolemia. Blood, 2010, 115(6), 1267-1276.
[http://dx.doi.org/10.1182/blood-2009-05-219808] [PMID: 19846887]
[33]
Su, Y.; Wang, Z.; Yang, H.; Cao, L.; Liu, F.; Bai, X.; Ruan, C. Clinical and molecular genetic analysis of a family with sitosterolemia and co-existing erythrocyte and platelet abnormalities. Haematologica, 2006, 91(10), 1392-1395.
[PMID: 17018391]
[34]
Kawamura, R.; Saiki, H.; Tada, H.; Hata, A. Acute myocardial infarction in a 25-year-old woman with sitosterolemia. J. Clin. Lipidol., 2018, 12(1), 246-249.
[http://dx.doi.org/10.1016/j.jacl.2017.10.017] [PMID: 29174072]
[35]
Othman, R.A.; Myrie, S.B.; Jones, P.J. Non-cholesterol sterols and cholesterol metabolism in sitosterolemia. Atherosclerosis, 2013, 231(2), 291-299.
[http://dx.doi.org/10.1016/j.atherosclerosis.2013.09.038] [PMID: 24267242]
[36]
Sabeva, N.S.; McPhaul, C.M.; Li, X.; Cory, T.J.; Feola, D.J.; Graf, G.A. Phytosterols differentially influence ABC transporter expression, cholesterol efflux and inflammatory cytokine secretion in macrophage foam cells. J. Nutr. Biochem., 2011, 22(8), 777-783.
[http://dx.doi.org/10.1016/j.jnutbio.2010.07.002] [PMID: 21111593]
[37]
Kolovou, G.; Voudris, V.; Drogari, E.; Palatianos, G.; Cokkinos, D.V. Coronary bypass grafts in a young girl with sitosterolemia. Eur. Heart J., 1996, 17(6), 965-966.
[http://dx.doi.org/10.1093/oxfordjournals.eurheartj.a014983] [PMID: 8781841]
[38]
Hansel, B.; Carrié, A.; Brun-Druc, N.; Leclert, G.; Chantepie, S.; Coiffard, A.S.; Kahn, J.F.; Chapman, M.J.; Bruckert, E. Premature atherosclerosis is not systematic in phytosterolemic patients: severe hypercholesterolemia as a confounding factor in five subjects. Atherosclerosis, 2014, 234(1), 162-168.
[http://dx.doi.org/10.1016/j.atherosclerosis.2014.02.030] [PMID: 24657386]
[39]
Goodyer, M.; Lovey, J.; Menétrey, M.J. Peripheral blood features of phytosterolaemia. Br. J. Haematol., 2015, 171(5), 669.
[http://dx.doi.org/10.1111/bjh.13626] [PMID: 26256107]
[40]
Kaya, Z.; Niu, D.M.; Yorulmaz, A.; Tekin, A.; Gürsel, T. A novel mutation of ABCG5 gene in a Turkish boy with phytosterolemia presenting with macrotrombocytopenia and stomatocytosis. Pediatr. Blood Cancer, 2014, 61(8), 1457-1459.
[http://dx.doi.org/10.1002/pbc.24934] [PMID: 24623560]
[41]
Greinacher, A.; Pecci, A.; Kunishima, S.; Althaus, K.; Nurden, P.; Balduini, C.L.; Bakchoul, T. Diagnosis of inherited platelet disorders on a blood smear: a tool to facilitate worldwide diagnosis of platelet disorders. J. Thromb. Haemost., 2017, 15(7), 1511-1521.
[http://dx.doi.org/10.1111/jth.13729] [PMID: 28457011]
[42]
Bastida Bermejo, J.M.; Hernández-Rivas, J.M.; González-Porras, J.R. Novel approaches for diagnosing inherited platelet disorders. Med. Clin. (Barc.), 2017, 148(2), 71-77.
[http://dx.doi.org/10.1016/j.medcli.2016.09.014] [PMID: 28218058]
[43]
Graf, G.A.; Cohen, J.C.; Hobbs, H.H. Missense mutations in ABCG5 and ABCG8 disrupt heterodimerization and trafficking. J. Biol. Chem., 2004, 279(23), 24881-24888.
[http://dx.doi.org/10.1074/jbc.M402634200] [PMID: 15054092]
[44]
Togo, M.; Toda, T.; Nguyen, L.A.; Kubota, S.; Tsukamoto, K.; Satoh, H.; Hara, M.; Iso-o, N.; Noto, H.; Kimura, S.; Nakahara, K.; Seyama, Y.; Hashimoto, Y. Genetic analysis of phytosterolaemia. J. Inherit. Metab. Dis., 2001, 24(1), 43-50.
[http://dx.doi.org/10.1023/A:1005650605042] [PMID: 11286381]
[45]
Heimerl, S.; Langmann, T.; Moehle, C.; Mauerer, R.; Dean, M.; Beil, F.U.; von Bergmann, K.; Schmitz, G. Mutations in the human ATP-binding cassette transporters ABCG5 and ABCG8 in sitosterolemia. Hum. Mutat., 2002, 20(2), 151.
[http://dx.doi.org/10.1002/humu.9047] [PMID: 12124998]
[46]
Kratz, M.; Kannenberg, F.; Gramenz, E.; Berning, B.; Trautwein, E.; Assmann, G.; Rust, S. Similar serum plant sterol responses of human subjects heterozygous for a mutation causing sitosterolemia and controls to diets enriched in plant sterols or stanols. Eur. J. Clin. Nutr., 2007, 61(7), 896-905.
[http://dx.doi.org/10.1038/sj.ejcn.1602598] [PMID: 17228349]
[47]
Bastida, J.M.; Lozano, M.L.; Benito, R.; Janusz, K.; Palma-Barqueros, V.; Del Rey, M.; Hernández-Sánchez, J.M.; Riesco, S.; Bermejo, N.; González-García, H.; Rodriguez-Alén, A.; Aguilar, C.; Sevivas, T.; López-Fernández, M.F.; Marneth, A.E.; van der Reijden, B.A.; Morgan, N.V.; Watson, S.P.; Vicente, V.; Hernández-Rivas, J.M.; Rivera, J.; González-Porras, J.R. Introducing high-throughput sequencing into mainstream genetic diagnosis practice in inherited platelet disorders. Haematologica, 2018, 103(1), 148-162.
[http://dx.doi.org/10.3324/haematol.2017.171132] [PMID: 28983057]
[48]
Bastida, J.M.; González-Porras, J.R.; Jiménez, C.; Benito, R.; Ordoñez, G.R.; Álvarez-Román, M.T.; Fontecha, M.E.; Janusz, K.; Castillo, D.; Fisac, R.M.; García-Frade, L.J.; Aguilar, C.; Martínez, M.P.; Bermejo, N.; Herrero, S.; Balanzategui, A.; Martin-Antorán, J.M.; Ramos, R.; Cebeiro, M.J.; Pardal, E.; Aguilera, C.; Pérez-Gutierrez, B.; Prieto, M.; Riesco, S.; Mendoza, M.C.; Benito, A.; Hortal Benito-Sendin, A.; Jiménez-Yuste, V.; Hernández-Rivas, J.M.; García-Sanz, R.; González-Díaz, M.; Sarasquete, M.E. Application of a molecular diagnostic algorithm for haemophilia A and B using next-generation sequencing of entire F8, F9 and VWF genes. Thromb. Haemost., 2017, 117(1), 66-74.
[http://dx.doi.org/10.1160/TH16-05-0375] [PMID: 27734074]
[49]
Bastida, J.M.; Del Rey, M.; Lozano, M.L.; Sarasquete, M.E.; Benito, R.; Fontecha, M.E.; Fisac, R.; García-Frade, L.J.; Aguilar, C.; Martínez, M.P.; Pardal, E.; Aguilera, C.; Pérez, B.; Ramos, R.; Cardesa, M.R.; Martin-Antorán, J.M.; Silvestre, L.A.; Cebeira, M.J.; Bermejo, N.; Riesco, S.; Mendoza, M.C.; García-Sanz, R.; González-Díaz, M.; Hernández-Rivas, J.M.; González-Porras, J.R. Design and application of a 23-gene panel by next-generation sequencing for inherited coagulation bleeding disorders. Haemophilia, 2016, 22(4), 590-597.
[http://dx.doi.org/10.1111/hae.12908] [PMID: 26879396]
[50]
Nurden, A.T.; Nurden, P. High-throughput sequencing for rapid diagnosis of inherited platelet disorders: a case for a European consensus. Haematologica, 2018, 103(1), 6-8.
[http://dx.doi.org/10.3324/haematol.2017.182295] [PMID: 29290630]
[51]
Salen, G.; Starc, T.; Sisk, C.M.; Patel, S.B. Intestinal cholesterol absorption inhibitor ezetimibe added to cholestyramine for sitosterolemia and xanthomatosis. Gastroenterology, 2006, 130(6), 1853-1857.
[http://dx.doi.org/10.1053/j.gastro.2006.02.027] [PMID: 16697747]
[52]
Othman, R.A.; Myrie, S.B.; Mymin, D.; Merkens, L.S.; Roullet, J.B.; Steiner, R.D.; Jones, P.J. Ezetimibe reduces plant sterol accumulation and favorably increases platelet count in sitosterolemia. J. Pediatr., 2015, 166(1), 125-131.
[http://dx.doi.org/10.1016/j.jpeds.2014.08.069] [PMID: 25444527]
[53]
Quintás-Cardama, A.; McCarthy, J.J. Long-term follow-up of a patient with sitosterolemia and hemolytic anemia with excellent response to ezetimibe. J. Genet. Disord. Genet. Rep., 2013, 2, 1.
[54]
Lozano, M.L.; Cook, A.; Bastida, J.M.; Paul, D.S.; Iruin, G.; Cid, A.R.; Adan-Pedroso, R.; Ramón González-Porras, J.; Hernández-Rivas, J.M.; Fletcher, S.J.; Johnson, B.; Morgan, N.; Ferrer-Marin, F.; Vicente, V.; Sondek, J.; Watson, S.P.; Bergmeier, W.; Rivera, J. Novel mutations in RASGRP2, which encodes CalDAG-GEFI, abrogate Rap1 activation, causing platelet dysfunction. Blood, 2016, 128(9), 1282-1289.
[http://dx.doi.org/10.1182/blood-2015-11-683102] [PMID: 27235135]
[55]
Sevivas, T.; Bastida, J.M.; Paul, D.S.; Caparros, E.; Palma-Barqueros, V.; Coucelo, M.; Marques, D.; Ferrer-Marín, F.; González-Porras, J.R.; Vicente, V.; Hernández-Rivas, J.M.; Watson, S.P.; Lozano, M.L.; Bergmeier, W.; Rivera, J. Identification of two novel mutations in RASGRP2 affecting platelet CalDAG-GEFI expression and function in patients with bleeding diathesis. Platelets, 2017, 1-4.
[http://dx.doi.org/10.1080/09537104.2017.1336214] [PMID: 28762304]

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