Page 131 - CIBERER2016-ENG

Most relevant scientific articles
• Jansen J.C., Cirak S., Van Scherpenzeel M., Timal S., Reunert J., Rust S. et al. CCDC115 Deficiency Causes a Disorder of Golgi Homeostasis with Abnormal Protein Glycosylation. American Journal of Human Genetics. 2016;98(2):310-321.
• Oyarzabal A., Bravo-Alonso I., Sanchez-Arago M., Rejas M.T., Merinero B., Garcia-Cazorla A.
et al. Mitochondrial response to the BCKDK-deficiency: Some clues to understand the positive dietary response in this form of autism. Biochimica et Biophysica Acta - Molecular Basis of Disease. 2016;1862(4):592-600.
• Gallego-Villar L., Rivera-Barahona A., Cuevas-Martin C., Guenzel A., Perez B., Barry M.A. et al. In vivo evidence of mitochondrial dysfunction and altered redox homeostasis in a genetic mouse model of propionic acidemia: Implications for the pathophysiology of this disorder. Free Radical Biology and Medicine. 2016; 96:1-12.
• Vega A.I., Medrano C., Navarrete R., Desviat L.R., Merinero B., Rodriguez-Pombo P. et al. Molecular diagnosis of glycogen storage disease and disorders with overlapping clinical symptoms by massive parallel sequencing. Genetics in Medicine. 2016;18(10):1037-1043.
• Yuste-Checa P., Brasil S., Gamez A., Underhaug J., Desviat L.R., Ugarte M. et al. Pharmacological Chaperoning: A Potential Treatment for PMM2-CDG. Human Mutation. 2016.
Hightlights
The research projects of the Diagnostic and Research of Inherited Metabolic diseases (IMD) are aimed to improve the diagnosis using cutting-edge genomic technologies and to develop therapeutic strategies based on the analysis of the mechanisms of action of the mutations identified. Concerning the advances
in diagnosis, the group has been able to improve the diagnosis rate by combination of comprehensive biochemical and cellular studies with functional analyzes of either exonic or intronic variants. In addition, the group participates in national and international networks of biochemical and genetic diagnosis for gathering and registry of patients sharing the same phenotype in order to gain clues for better diagnosis. At the genetic level we highlight the study, for the first time in our country, of patients diagnosed with glycogen storage disorders (GSD) by massive parallel sequencing. In addition to the diagnosis of GSD patients we highlight the detection of mutations in other genes sharing phenotypic characteristics with GSD (hepatic, cardiac and / or muscular alterations), resulting in an erroneous initial diagnostic suspicion. On the other hand we have been actively involved in the identification of a new CDG-causing gene (CCDC115). The results obtained after functional cellular, biochemical and clinical analysis suggests that this gene is involved in Golgi trafficking. Regarding the therapeutic research we highlight the studies of pathophysiology, using animal and cellular models of propionic aciduria and deficiency of BCKDK disorders. In both cases the results show that therapies aimed to avoid oxidative damage and targeted for recovering mitochondrial function and biogenesis could be beneficial in combination with current conventional therapies. Finally, after the screening of a library of 10000 compounds we have described a promising chemical structure as a starting point for the development of new therapeutic agents to treat destabilizing mutations identified on PMM2-CDG disease.
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