CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in RASGRP2

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 deficienc...

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Autores principales:	Sara Morais, Mónica Pereira, Catarina Lau, Ana Gonçalves, Catarina Monteiro, Marta Gonçalves, Jorge Oliveira, Lurdes Moreira, Eugénia Cruz, Rosário Santos, Margarida Lima
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	platelets <i>RASGRP2</i> CalDAG-GEFI deficiency platelet function diseases Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/a405991a6b0f42dc875ca6672994f245
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spelling	oai:doaj.org-article:a405991a6b0f42dc875ca6672994f2452021-11-25T17:56:31ZCalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in <i>RASGRP2</i>10.3390/ijms2222124231422-00671661-6596https://doaj.org/article/a405991a6b0f42dc875ca6672994f2452021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12423https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067<i>RASGRP2</i> 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 <i>RASGRP2</i> 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 <i>RASGRP2</i> (c.999G>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 <i>RASGRP2</i> variant reported herein, there is a phenotypic expression, albeit milder, in heterozygous carriers.Sara MoraisMónica PereiraCatarina LauAna GonçalvesCatarina MonteiroMarta GonçalvesJorge OliveiraLurdes MoreiraEugénia CruzRosário SantosMargarida LimaMDPI AGarticleplatelets<i>RASGRP2</i>CalDAG-GEFI deficiencyplatelet function diseasesBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12423, p 12423 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	platelets <i>RASGRP2</i> CalDAG-GEFI deficiency platelet function diseases Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	platelets <i>RASGRP2</i> CalDAG-GEFI deficiency platelet function diseases Biology (General) QH301-705.5 Chemistry QD1-999 Sara Morais Mónica Pereira Catarina Lau Ana Gonçalves Catarina Monteiro Marta Gonçalves Jorge Oliveira Lurdes Moreira Eugénia Cruz Rosário Santos Margarida Lima CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in <i>RASGRP2</i>
description	<i>RASGRP2</i> 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 <i>RASGRP2</i> 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 <i>RASGRP2</i> (c.999G>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 <i>RASGRP2</i> variant reported herein, there is a phenotypic expression, albeit milder, in heterozygous carriers.
format	article
author	Sara Morais Mónica Pereira Catarina Lau Ana Gonçalves Catarina Monteiro Marta Gonçalves Jorge Oliveira Lurdes Moreira Eugénia Cruz Rosário Santos Margarida Lima
author_facet	Sara Morais Mónica Pereira Catarina Lau Ana Gonçalves Catarina Monteiro Marta Gonçalves Jorge Oliveira Lurdes Moreira Eugénia Cruz Rosário Santos Margarida Lima
author_sort	Sara Morais
title	CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in <i>RASGRP2</i>
title_short	CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in <i>RASGRP2</i>
title_full	CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in <i>RASGRP2</i>
title_fullStr	CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in <i>RASGRP2</i>
title_full_unstemmed	CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in <i>RASGRP2</i>
title_sort	caldag-gefi deficiency in a family with symptomatic heterozygous and homozygous carriers of a likely pathogenic variant in <i>rasgrp2</i>
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a405991a6b0f42dc875ca6672994f245
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CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in <i>RASGRP2</i>

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