{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T23:23:18Z","timestamp":1768000998369,"version":"3.49.0"},"reference-count":16,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T00:00:00Z","timestamp":1637107200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>RASGRP2 encodes the calcium and diacylglycerol (DAG)-regulated guanine nucleotide exchange factor I (CalDAG-GEFI) identified as a Rap1-activating molecule. Pathogenic variants previously identified in RASGRP2 allowed the characterization of CalDAG-GEFI deficiency as a non-syndromic, autosomal recessive platelet function disease. We report on the clinical manifestations and laboratory features of a Portuguese family with a likely pathogenic variant in RASGRP2 (c.999G&gt;C leading to a p.Lys333Asn change in the CDC25 catalytic domain of CalDAG-GEFI) and discuss the contribution of this variant to the disease manifestations. Based on the study of this family with one homozygous patient and five heterozygous carriers and on a critical analysis of the literature, we challenge previous knowledge that CalDAG-GEFI deficiency only manifests in homozygous patients. Our data suggest that at least for the RASGRP2 variant reported herein, there is a phenotypic expression, albeit milder, in heterozygous carriers.<\/jats:p>","DOI":"10.3390\/ijms222212423","type":"journal-article","created":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T21:32:07Z","timestamp":1637184727000},"page":"12423","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in RASGRP2"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4266-4457","authenticated-orcid":false,"given":"Sara","family":"Morais","sequence":"first","affiliation":[{"name":"Setor de Trombose e Hemostase, Servi\u00e7o de Hematologia Cl\u00ednica, Hospital de Santo Ant\u00f3nio (HSA), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-001 Porto, Portugal"},{"name":"UMIB\u2014Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica, ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-131 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3346-0543","authenticated-orcid":false,"given":"M\u00f3nica","family":"Pereira","sequence":"additional","affiliation":[{"name":"Setor de Trombose e Hemostase, Servi\u00e7o de Hematologia Cl\u00ednica, Hospital de Santo Ant\u00f3nio (HSA), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-001 Porto, Portugal"},{"name":"UMIB\u2014Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica, ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-131 Porto, Portugal"}]},{"given":"Catarina","family":"Lau","sequence":"additional","affiliation":[{"name":"UMIB\u2014Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica, ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-131 Porto, Portugal"},{"name":"Laborat\u00f3rio de Citometria, Servi\u00e7o de Hematologia Cl\u00ednica, Hospital de Santo Ant\u00f3nio (HSA), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-001 Porto, Portugal"}]},{"given":"Ana","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"UMIB\u2014Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica, ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-131 Porto, Portugal"},{"name":"Unidade de Gen\u00e9tica Molecular, Centro de Gen\u00e9tica M\u00e9dica Doutor Jacinto Magalh\u00e3es (CGMJM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4050-466 Porto, Portugal"}]},{"given":"Catarina","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Setor de Trombose e Hemostase, Servi\u00e7o de Hematologia Cl\u00ednica, Hospital de Santo Ant\u00f3nio (HSA), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-001 Porto, Portugal"},{"name":"UMIB\u2014Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica, ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-131 Porto, Portugal"}]},{"given":"Marta","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"UMIB\u2014Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica, ICBAS\u2014Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, 4050-131 Porto, Portugal"},{"name":"Laborat\u00f3rio de Citometria, Servi\u00e7o de Hematologia Cl\u00ednica, Hospital de Santo Ant\u00f3nio (HSA), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-001 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3924-6385","authenticated-orcid":false,"given":"Jorge","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Unidade de Gen\u00e9tica Molecular, Centro de Gen\u00e9tica M\u00e9dica Doutor Jacinto Magalh\u00e3es (CGMJM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4050-466 Porto, Portugal"}]},{"given":"Lurdes","family":"Moreira","sequence":"additional","affiliation":[{"name":"Setor de Trombose e Hemostase, Servi\u00e7o de Hematologia Cl\u00ednica, Hospital de Santo Ant\u00f3nio (HSA), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-001 Porto, Portugal"}]},{"given":"Eug\u00e9nia","family":"Cruz","sequence":"additional","affiliation":[{"name":"Setor de Trombose e Hemostase, Servi\u00e7o de Hematologia Cl\u00ednica, Hospital de Santo Ant\u00f3nio (HSA), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-001 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8594-6377","authenticated-orcid":false,"given":"Ros\u00e1rio","family":"Santos","sequence":"additional","affiliation":[{"name":"UMIB\u2014Unidade Multidisciplinar de Investiga\u00e7\u00e3o Biom\u00e9dica, ICBAS\u2014Instituto de Ci\u00eancias 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