Characterization of the molecular bases of the diseases with neurodegeneration with brain iron accumulation and related movement disorders. Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited neurologic disorders in which iron accumulates in the brain, and patients present with ataxia, dystonia, spasticity, parkinsonism, and additional clinical signs. NBIA disorders are rare diseases with a prevalence of 1-3/1 000 000. The main aims are: (i) To characterize the underlying molecular bases; (ii) To identify the microRNA profile that could be useful for prognosis; and (iii) To generate a CPC (Cerebellum Purkinje Cell) model from patients’ iPSCs that replicates the pathophysiology of the disease with the aim to search for therapies.
Genetic epidemiology, characterization of the microRNA profile and the microbiote associated with the Wilson’s disease. The Wilson’s 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 project includes three approaches: (i) To characterize genetically the WD patients from the Valencian Land and to gain insight into the genetic epidemiology; (ii) To identify the microRNA profile that could be useful for prognosis; and (iii) To define the intestinal flora and to investigate its contribution to the clinical picture.
Molecular bases which underlie hereditary motor and/or sensory neuropathy. This group of diseases shows a wide genetic heterogeneity: more than 80 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.
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 transcriptional repression and lipogenesis. 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.