Details

Autor(en) / Beteiligte

• Boissel, Sarah
• Reish, Orit
• Proulx, Karine
• Kawagoe-Takaki, Hiroko
• Sedgwick, Barbara
• Yeo, Giles S.H.
• Meyre, David
• Golzio, Christelle
• Molinari, Florence
• Kadhom, Noman
• Etchevers, Heather C.
• Saudek, Vladimir
• Farooqi, I. Sadaf
• Froguel, Philippe
• Lindahl, Tomas
• O'Rahilly, Stephen
• Munnich, Arnold
• Colleaux, Laurence

Titel

Loss-of-Function Mutation in the Dioxygenase-Encoding FTO Gene Causes Severe Growth Retardation and Multiple Malformations

Ist Teil von

• American journal of human genetics, 2009-07, Vol.85 (1), p.106-111

Ort / Verlag

Cambridge, MA: Elsevier Inc

Erscheinungsjahr

2009

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.