Genetics and Genomics of Neuromuscular and Neurodegenerative Disorders
Characterization of the molecular bases of the neurodegeneration with brain iron accumulation disorders. Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the brain, mainly in the basal ganglia. NBIA disorders are rare diseases with a prevalence of 1-3/1,000,000. Ten genes are associated with this group of diseases. The main aims are: (i) to characterize genetically the Spanish population of NBIA patients; and (ii) to identify the microRNA profile that could be useful for prognosis and new therapies.
Genetic epidemiology, identification of genetic modifiers and characterization of the microRNA profile associated with the Wilson disease.The Wilson disease (WD) is a rare disorder with an estimated prevalence of 1/30,000. The WD is caused by a progressive accumulation of copper in the organism, caused by an abnormal activity of the protein encoded by the ATP7B gene, which transports copper into bile and incorporates it into ceruloplasmin. The research prohect includes three approaches: (i) to characterize genetically the WD patients from the Valencian Land and to gain insight into the genetic epidemiology; (ii) to characterize genetic variants that could modify the phenotype of WD patients; and (iii) to identify the microRNA profile that could be useful for prognosis and new therapies for WD.
Molecular bases which underlie hereditary motor and/or sensory neuropathy. This group of diseases shows a wide genetic heterogeneity: more than 60 genes have been reported and this figure does not cease to increase. The characterization of the genetic bases of these neuropathies is investigated with different approaches: analysis gene-by-gene of the genes that are more frequently involved or candidate genes using Sanger sequencing; panel of genes that makes possible the analysis of all the genes described by massive sequencing; and exome sequencing and/or genome-wide mapping with the aim of identifying new genes involved in this group of diseases.
To characterize the MORC2 gene involved in a new form of Charcot-Marie-Tooth disease. In our series, three families carry mutations in a gene not previously related to neuropathies. Little is known about the function of MORC2 gene. It has been proposed that MORC2 may play a role in processes related to DNA-damage response. We currently work on the characterization of this gene and on the analysis of the detected mutations in order to explain how this nucleotide change leads to disease, by investigating its gene expression and its interactome network.
To investigate the cellular pathophysiology of the Charcot-Marie-Tooth disease type 4C (CMT4C).SH3TC2, the protein associated with CMT4C, takes part in multiprotein complex, related to the signal transduction from axon to Schawnn cell. Our research is focused in the signaling pathways and interactors of SH3TC2 to gain insight into the role of this protein in the development of peripheral nerves.
The Drosophila junctophilin gene is functionally equivalent to its four mammalian counterparts and is a modifier of a Huntingtin poly-Q expansion and the Notch pathway.
Calpena E, López Del Amo V, Chakraborty M, Llamusí B, Artero R, Espinós C, Galindo MI
Disease models & mechanisms , 2018 Jan 17, vol. 11
A newly distal hereditary motor neuropathy caused by a rare AIFM1 mutation.
Sancho P, Sánchez-Monteagudo A, Collado A, Marco-Marín C, Domínguez-González C, Camacho A, Knecht E, Espinós C, Lupo V
Neurogenetics , 2017 Dec, vol. 18, pag. 245-250
Assessment of Targeted Next-Generation Sequencing as a Tool for the Diagnosis of Charcot-Marie-Tooth Disease and Hereditary Motor Neuropathy.
Lupo V, García-García F, Sancho P, Tello C, García-Romero M, Villarreal L, Alberti A, Sivera R, Dopazo J, Pascual-Pascual SI, Márquez-Infante C, Casasnovas C, Sevilla T, Espinós C
The Journal of molecular diagnostics : JMD , 2016 Mar, vol. 18, pag. 225-34
Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease.
Sevilla T, Lupo V, Martínez-Rubio D, Sancho P, Sivera R, Chumillas MJ, García-Romero M, Pascual-Pascual SI, Muelas N, Dopazo J, Vílchez JJ, Palau F, Espinós C
Brain : a journal of neurology , 2016 Jan, vol. 139, pag. 62-72
Junctophilin-1 is a modifier gene of GDAP1-related Charcot-Marie-Tooth disease.
Pla-Martín D, Calpena E, Lupo V, Márquez C, Rivas E, Sivera R, Sevilla T, Palau F, Espinós C
Human molecular genetics , 2015 Jan 1, vol. 24, pag. 213-29