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FTO variant associated with malformation syndrome
Author(s) -
Rohena Luis,
Lawson Michelle,
Guzman Edwin,
Ganapathi Mythily,
Cho Megan T.,
Haverfield Eden,
AnyaneYeboa Kwame
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37515
Subject(s) - phenotype , loss function , craniosynostosis , mutation , genetics , medicine , biology , gene
Common FTO variants are associated with obesity. However, it has recently been shown that homozygous FTO c.947G>A variant, which predicts p.R316Q, and c.956C>T, which predicts p.S319F, are associated with a malformation syndrome inherited in an autosomal recessive pattern. We present a similar homozygous FTO c.965G>A variant that predicts p.R322Q, associated with a lethal malformation syndrome in a consanguineous Yemeni family. Functional studies showed that the p.R316Q, p.S219F, and p.R322Q variants render the FTO protein inactive. We further expand on the phenotype of homozygous FTO loss‐of‐function mutations to include eye abnormalities, gingival overgrowth, craniosynostosis, and cutaneous photosensitivity. © 2015 Wiley Periodicals, Inc.