2. Academic Validation
  3. Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations

Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations

  • Am J Hum Genet. 2009 Jul;85(1):106-11. doi: 10.1016/j.ajhg.2009.06.002.
Sarah Boissel 1,  Orit Reish,  Karine Proulx,  Hiroko Kawagoe-Takaki,  Barbara Sedgwick,  Giles S H Yeo,  David Meyre,  Christelle Golzio,  Florence Molinari,  Noman Kadhom,  Heather C Etchevers,  Vladimir Saudek,  I Sadaf Farooqi,  Philippe Froguel,  Tomas Lindahl,  Stephen O'Rahilly,  Arnold Munnich,  Laurence Colleaux
Affiliations

Affiliation

  • 1 INSERM U781 and Département de Génétique, Université Paris Descartes, Hôpital Necker-Enfants Malades, 75015 Paris, France.
PMID: 19559399 DOI: 10.1016/j.ajhg.2009.06.002
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.

Figures