Instruct: Identify the main category of Medrxiv papers based on the titles and abstracts
Query: A rare congenital anemia is caused by mutations in the centralspindlin complex Congenital dyserythropoietic anemias (CDAs) are rare disorders characterized by morphologic abnormalities of erythroid precursors leading to ineffective erythropoiesis. CDA type III (CDAIII), characterized by erythroblast multinucleation, represents the rarest form with only [~]60 patients described in the literature. Previous work, studying two independent families, identified a causative dominant missense mutation in KIF23, which encodes for the kinesin MKLP1. Here, we describe a sporadic CDAIII case associated with compound heterozygous variants in RACGAP1, a gene not previously associated with any disease. RACGAP1 encodes CYK4, a GTPase activating protein (GAP) for Rho-family GTPases, which interacts with MKLP1 to form the centralspindlin complex. Functional assays show these RACGAP1 variants cause cytokinesis defects due, at least in part, to altering the substrate specificities of the GAP activity of CYK4. These findings provide novel insights into the structural determinants of the GAP activity and demonstrates that cytokinesis failure due to centralspindlin defects leads to CDAIII. Our findings highlight the importance of viewing diseases as malfunctions of common biological pathways/complexes and suggests that next-generation sequencing analysis pipelines should integrate a systems approach in order to identify such functionally related variants.
19
The categories of this paper are: public
34
The categories of this paper are: therapy
14
The categories of this paper are: cardiovascular
43
The categories of this paper are: environmental
37
The categories of this paper are: aids
5
The categories of this paper are: health
15
The categories of this paper are: allergy
63
The categories of this paper are: pain
11
The categories of this paper are: policy
29
The categories of this paper are: anesthesia
41
The categories of this paper are: nephrology
25
The categories of this paper are: improvement
55
The categories of this paper are: obstetrics
18
The categories of this paper are: global
73
The categories of this paper are: toxicology
9
The categories of this paper are: diseases