GERMLINE MUTATIONS IN WNK2 COULD BE ASSOCIATED WITH SERRATED POLYPOSIS SYNDROME, Soares de Lima et al.

Patients with serrated polyposis syndrome (SPS) have multiple and/or large serrated colonic polyps and higher risk for colorectal cancer. Our main aim was to identify the inherited genetic basis of this disease. We performed germline exome sequencing in 39 SPS patients from 16 families and sequenced specific genes in an independent cohort of 211 unrelated SPS cases. Additional 297 SPS cases were also available for further replication. We identified 15 rare germline variants in the WNK2 gene in 17 SPS patients. In a WNK2-disrupted cell model transfected with the variants of interest, we detected alterations in the MAPK pathway, cell cycle progression, survival and adhesion. We postulate that germline WNK2 variants may be implicated in inherited predisposition to SPS, being the disruption of the role of WNK2 as a MAPK regulator the plausible underlying mechanism. (By Dr. Sergi Castellví-Bel, https://jmg.bmj.com/content/early/2022/10/21/jmg-2022-108684 )

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