title: FTO variant associated with malformation syndrome.
abstract: 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.
authors.affiliation: Division of Clinical Genetics, Department of Pediatrics, Columbia University Medical Center, New York, New York.|Division of Medical Genetics, Department of Pediatrics, San Antonio Military Medical Center, San Antonio, Texas.
authors.forename: Luis
authors.initials: L
authors.lastname: Rohena
authors.affiliation: Department of Pediatrics, San Antonio Military Medical Center, San Antonio, Texas.
authors.forename: Michelle
authors.initials: M
authors.lastname: Lawson
authors.affiliation: Division of Clinical Genetics, Department of Pediatrics, Columbia University Medical Center, New York, New York.
authors.forename: Edwin
authors.initials: E
authors.lastname: Guzman
authors.affiliation: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York.
authors.forename: Mythily
authors.initials: M
authors.lastname: Ganapathi
authors.affiliation: GeneDx, Gaithersburg, Maryland.
authors.forename: Megan T
authors.initials: MT
authors.lastname: Cho
authors.affiliation: GeneDx, Gaithersburg, Maryland.
authors.forename: Eden
authors.initials: E
authors.lastname: Haverfield
authors.affiliation: Division of Clinical Genetics, Department of Pediatrics, Columbia University Medical Center, New York, New York.
authors.forename: Kwame
authors.initials: K
authors.lastname: Anyane-Yeboa
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics*; D001921:Brain / Q000473:pathology; D005260:Female; D014644:Genetic Variation; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype; D013577:Syndrome; D014057:Tomography, X-Ray Computed
chemical_list: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human
keywords: exome sequencing; fat mass-and obesity-associated gene (FTO); multiple congenital anomalies; variant mutation