Mutations in the fatty acid transport protein 4 gene cause the ichthyosis prematurity syndrome.

Published on Aug 14, 2009in American Journal of Human Genetics10.502
· DOI :10.1016/J.AJHG.2009.06.021
Joakim Klar32
Estimated H-index: 32
(Uppsala University),
Martina Schweiger28
Estimated H-index: 28
(University of Graz)
+ 7 AuthorsJudith Fischer49
Estimated H-index: 49
Ichthyosis prematurity syndrome (IPS) is an autosomal-recessive disorder characterized by premature birth and neonatal asphyxia, followed by a lifelong nonscaly ichthyosis with atopic manifestations. Here we show that the gene encoding the fatty acid transport protein 4 (FATP4) is mutated in individuals with IPS. Fibroblasts derived from a patient with IPS show reduced activity of very long-chain fatty acids (VLCFA)-CoA synthetase and a specific reduction in the incorporation of VLCFA into cellular lipids. The human phenotype is consistent with Fatp4 deficiency in mice that is characterized by a severe skin phenotype, a defective permeability barrier function, and perturbed VLCFA metabolism. Our results further emphasize the importance of fatty acid metabolism for normal epidermal barrier function illustrated by deficiency of a member in the FATP family of proteins.
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