New gene identified whose mutations cause a fatal mitochondrial encephalopathy

An article in the American Journal of Human Genetics identifies a new gene whose mutations cause a fatal childhood disease with encephalopathy and pulmonary hypertension, being usual that patients die before 15 months. The team that signed the article is directed by Dr. Antònia Ribes, and comprised by: A. Navarro-Sastre, F. Tort, A. Font, J. García-Villoria and P. Briones, from the Section of Congenital Metabolic Errors - IBC Department of Biochemistry and Molecular Genetics, Hospital Clínic - IDIBAPS of Barcelona.

The gene NFU1, that codifies a protein containing iron-sulfur clusters, is believed to be involved in the biosynthesis of lipoic acid. This involvement was suggested and later demonstrated by the biochemical phenotype of patients. Using cellular models, the authors showed that the NFU1 protein was necessary as sulfur donor for the biosynthesis of lipoic acid. Studies in yeast homologues revealed the pathogenicity of the mutation found in patients as well as the possible mechanism by which it can affect NFU1 protein function.

This is the first gene demonstrated to be involved in lipoic acid biosynthesis in humans. The clinical description, biochemistry and genetics of the disease opens the door to finding new genes involved in this biosynthesis, and the future design of new therapeutic strategies. This work, in which researchers collaborated with other Spanish hospitals, as well as the Hadash University of Jerusalem and the University of Marburg, has been published in the American Journal of Human Genetics.