title: Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations.
abstract: FTO is a nuclear protein belonging to the AlkB-related non-haem iron- and 2-oxoglutarate-dependent dioxygenase family. Although polymorphisms within the first intron of the FTO gene have been associated with obesity, the physiological role of FTO remains unknown. Here we show that a R316Q mutation, inactivating FTO enzymatic activity, is responsible for an autosomal-recessive lethal syndrome. Cultured skin fibroblasts from affected subjects showed impaired proliferation and accelerated senescence. These findings indicate that FTO is essential for normal development of the central nervous and cardiovascular systems in human and establish that a mutation in a human member of the AlkB-related dioxygenase family results in a severe polymalformation syndrome.
authors: INSERM U781 and Département de Génétique, Université Paris Descartes, Hôpital Necker-Enfants Malades, 75015 Paris, France.
authors: Sarah
authors: S
authors: Boissel
authors: Orit
authors: O
authors: Reish
authors: Karine
authors: K
authors: Proulx
authors: Hiroko
authors: H
authors: Kawagoe-Takaki
authors: Barbara
authors: B
authors: Sedgwick
authors: Giles S H
authors: GS
authors: Yeo
authors: David
authors: D
authors: Meyre
authors: Christelle
authors: C
authors: Golzio
authors: Florence
authors: F
authors: Molinari
authors: Noman
authors: N
authors: Kadhom
authors: Heather C
authors: HC
authors: Etchevers
authors: Vladimir
authors: V
authors: Saudek
authors: I Sadaf
authors: IS
authors: Farooqi
authors: Philippe
authors: P
authors: Froguel
authors: Tomas
authors: T
authors: Lindahl
authors: Stephen
authors: S
authors: O'Rahilly
authors: Arnold
authors: A
authors: Munnich
authors: Laurence
authors: L
authors: Colleaux
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000595:Amino Acid Sequence; D000818:Animals; D020022:Genetic Predisposition to Disease; D006130:Growth Disorders / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human