CalDAG-GEFI Deficiency in a Family with Symptomatic Heterozygous and Homozygous Carriers of a Likely Pathogenic Variant in RASGRP2.
Sara MoraisMónica PereiraCatarina LauAna GonçalvesCatarina MonteiroMarta GonçalvesJorge OliveiraLurdes MoreiraEugénia CruzRosário SantosMargarida LimaPublished in: International journal of molecular sciences (2021)
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.
Keyphrases
- early onset
- end stage renal disease
- ejection fraction
- intellectual disability
- poor prognosis
- newly diagnosed
- replacement therapy
- chronic kidney disease
- systematic review
- healthcare
- signaling pathway
- gene expression
- case report
- copy number
- prognostic factors
- transcription factor
- big data
- cell proliferation
- autism spectrum disorder
- machine learning
- patient reported outcomes
- smoking cessation
- binding protein
- artificial intelligence