FTO variant associated with malformation syndrome.

Common FTOvariants are associated with obesity. However, it has recently been shown that homozygous FTOc.947G>A variant, which predicts p.R316Q, and c.956C>T, which predicts p.S319F, are associated with a malformation syndromeinherited in an autosomal recessive pattern. We present a similar homozygous FTOc.965G>A variant that predicts p.R322Q, associated with a lethal malformation syndromein a consanguineousYemeni family. Functional studies showed that the p.R316Q, p.S219F, and p.R322Q variants render the FTOprotein inactive. We further expand on the phenotype of homozygous FTOloss-of-function mutations to include eye abnormalities, gingival overgrowth, craniosynostosis, and cutaneous photosensitivity. © 2015 Wiley Periodicals, Inc.