Cargando…
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 deficiency as a non-syndromic, autosomal recess...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618213/ https://www.ncbi.nlm.nih.gov/pubmed/34830306 http://dx.doi.org/10.3390/ijms222212423 |
_version_ | 1784604693500002304 |
---|---|
author | Morais, Sara Pereira, Mónica Lau, Catarina Gonçalves, Ana Monteiro, Catarina Gonçalves, Marta Oliveira, Jorge Moreira, Lurdes Cruz, Eugénia Santos, Rosário Lima, Margarida |
author_facet | Morais, Sara Pereira, Mónica Lau, Catarina Gonçalves, Ana Monteiro, Catarina Gonçalves, Marta Oliveira, Jorge Moreira, Lurdes Cruz, Eugénia Santos, Rosário Lima, Margarida |
author_sort | Morais, Sara |
collection | PubMed |
description | 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>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. |
format | Online Article Text |
id | pubmed-8618213 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86182132021-11-27 CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in RASGRP2 Morais, Sara Pereira, Mónica Lau, Catarina Gonçalves, Ana Monteiro, Catarina Gonçalves, Marta Oliveira, Jorge Moreira, Lurdes Cruz, Eugénia Santos, Rosário Lima, Margarida Int J Mol Sci Case Report 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>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. MDPI 2021-11-17 /pmc/articles/PMC8618213/ /pubmed/34830306 http://dx.doi.org/10.3390/ijms222212423 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Case Report Morais, Sara Pereira, Mónica Lau, Catarina Gonçalves, Ana Monteiro, Catarina Gonçalves, Marta Oliveira, Jorge Moreira, Lurdes Cruz, Eugénia Santos, Rosário Lima, Margarida CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in RASGRP2 |
title | CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in RASGRP2 |
title_full | CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in RASGRP2 |
title_fullStr | CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in RASGRP2 |
title_full_unstemmed | CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in RASGRP2 |
title_short | CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in RASGRP2 |
title_sort | caldag-gefi deficiency in a family with symptomatic heterozygous and homozygous carriers of a likely pathogenic variant in rasgrp2 |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618213/ https://www.ncbi.nlm.nih.gov/pubmed/34830306 http://dx.doi.org/10.3390/ijms222212423 |
work_keys_str_mv | AT moraissara caldaggefideficiencyinafamilywithsymptomaticheterozygousandhomozygouscarriersofalikelypathogenicvariantinrasgrp2 AT pereiramonica caldaggefideficiencyinafamilywithsymptomaticheterozygousandhomozygouscarriersofalikelypathogenicvariantinrasgrp2 AT laucatarina caldaggefideficiencyinafamilywithsymptomaticheterozygousandhomozygouscarriersofalikelypathogenicvariantinrasgrp2 AT goncalvesana caldaggefideficiencyinafamilywithsymptomaticheterozygousandhomozygouscarriersofalikelypathogenicvariantinrasgrp2 AT monteirocatarina caldaggefideficiencyinafamilywithsymptomaticheterozygousandhomozygouscarriersofalikelypathogenicvariantinrasgrp2 AT goncalvesmarta caldaggefideficiencyinafamilywithsymptomaticheterozygousandhomozygouscarriersofalikelypathogenicvariantinrasgrp2 AT oliveirajorge caldaggefideficiencyinafamilywithsymptomaticheterozygousandhomozygouscarriersofalikelypathogenicvariantinrasgrp2 AT moreiralurdes caldaggefideficiencyinafamilywithsymptomaticheterozygousandhomozygouscarriersofalikelypathogenicvariantinrasgrp2 AT cruzeugenia caldaggefideficiencyinafamilywithsymptomaticheterozygousandhomozygouscarriersofalikelypathogenicvariantinrasgrp2 AT santosrosario caldaggefideficiencyinafamilywithsymptomaticheterozygousandhomozygouscarriersofalikelypathogenicvariantinrasgrp2 AT limamargarida caldaggefideficiencyinafamilywithsymptomaticheterozygousandhomozygouscarriersofalikelypathogenicvariantinrasgrp2 |