Inherited bleeding disorders

Gene: PTPRJ

I don't know

Marconi C et al. Dec 2018 (PMID: 30591527) through exome sequencing of two siblings with autosomal recessive thrombocytopenia, identified two biallelic loss-of-function variants in the gene PTPRJ. They also investigated the pathogenic role of PTPRJ deficiency in hematopoiesis in vivo, carried out using CRISPR/Cas9-mediated ablation of ptprja (the ortholog of human PTPRJ) in zebrafish, which induced a significantly decreased number of CD41+ thrombocytes in vivo. Megakaryocytes of the patients showed impaired maturation and profound defects in SDF1-driven migration and formation of proplatelets in vitro. Silencing of PTPRJ in a human megakaryocytic cell line reproduced the functional defects observed in patients' megakaryocytes. The disorder caused by PTPRJ mutations presented as a non-syndromic thrombocytopenia characterized by spontaneous bleeding, small-sized platelets, and impaired platelet responses to the GPVI agonists collagen and convulxin.
Sources: Literature

Created: 7 Jan 2019, 10:50 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Thrombocytopenia; spontaneous bleeding, small-sized platelets, and impaired platelet responses to the GPVI agonists collagen and convulxin.

Publications

• 30591527