Evidence suggests that germline RNF43 mutations are a rare cause of serrated polyposis

We read with interest the work by Yan et al published in Gut.1 The serrated (hyperplastic) polyposis syndrome (SPS) is a heterogeneous disease defined by the presence of multiple serrated polyps throughout the colon,2 causing an increased risk (16%) of colorectal cancer (CRC).3 By performing whole-exome sequencing in 20 SPS families, Gala et al identified a germline mutation, c.338C>A (p.R113*), in the RING-type E3 ubiquitin ligase RNF43, an inhibitor of the Wnt pathway, in two independent families.4 The c.394C>T (p.R132*) mutation was subsequently identified in two SPS-affected members of one family, supporting a causal role in SPS.5 In the study by Yan et al whole-exome sequence analysis of four SPS families identified a deleterious germline mutation, c.953–1G>A (p.E318fs), in six members of one family, five fulfilling the WHO criteria for SPS.1 Buchanan et al assessed the mutation status of...

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