A5031544799- Hereditary Neurological Disorders
- Genetic Neurodegenerative Diseases
- Neurological diseases and metabolism
- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Hearing, Cochlea, Tinnitus, Genetics
- Trace Elements in Health
- Genomics and Rare Diseases
- Botulinum Toxin and Related Neurological Disorders
- RNA regulation and disease
- Neurogenetic and Muscular Disorders Research
- Heavy Metal Exposure and Toxicity
- Coenzyme Q10 studies and effects
- Endoplasmic Reticulum Stress and Disease
- Iron Metabolism and Disorders
- Folate and B Vitamins Research
- Platelet Disorders and Treatments
- Blood groups and transfusion
- Cancer-related gene regulation
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Neurological disorders and treatments
- Hippo pathway signaling and YAP/TAZ
- Hemophilia Treatment and Research
- Celiac Disease Research and Management
Centre for Biomedical Network Research on Rare Diseases
2011-2024
Instituto de Investigación Sanitaria La Fe
2012-2024
Centro de Investigacion Principe Felipe
2015-2024
Instituto de Salud Carlos III
2007-2024
Universitat Politècnica de València
2023-2024
Instituto de Investigación de Enfermedades Raras
2009-2023
Universitat de València
2000-2023
INCLIVA Health Research Institute
2016-2023
Valencia Catholic University Saint Vincent Martyr
2022-2023
Universidad Cardenal Herrera CEU
2022
To determine the genetic distribution and phenotypic correlation of an extensive series patients with Charcot-Marie-Tooth disease in a geographically well-defined Mediterranean area.A thorough screening, including most known genes involved this disease, was performed analyzed longitudinal descriptive study. Clinical data were compared among subgroups.Molecular diagnosis accomplished 365 438 (83.3%), higher success rate demyelinating forms disease. The CMT1A duplication (PMP22 gene) frequent...
Cranial nerve involvement in Charcot-Marie-Tooth disease (CMT) is rare, though there are a number of CMT syndromes which vocal cord paralysis characteristic feature. due to mutations the ganglioside-induced differentiation-associated protein 1 gene (GDAP1) has been reported be associated with and diaphragmatic palsy. In order address prevalence these complications patients GDAP1 we evaluated respiratory function nine from eight unrelated families this disorder. Hoarseness voice inability...
Charcot-Marie-Tooth disease (CMT) is a complex disorder with wide genetic heterogeneity. Here we present new axonal form, associated the gene microrchidia family CW-type zinc finger 2 (MORC2). Whole-exome sequencing in autosomal dominant segregation identified novel MORC2 p.R190W change four patients. Further mutational screening our clinical series detected two additional sporadic cases, one patient who also carried same mutation and another that harboured p.S25L mutation. Genetic silico...
Abstract Background and purpose Distal hereditary motor neuropathies (dHMNs) are a heterogeneous group of disorders characterized by degeneration the component peripheral nerves. Currently, only 15% to 32.5% patients with dHMN genetically. Additionally, prevalence these genetic is not well known. Recently, biallelic mutations in sorbitol dehydrogenase gene ( SORD ) have been identified as cause dHMN, an estimated frequency undiagnosed cases up 10%. Methods In present study, we included 163...
The knowledge of the genetic variability local population is utmost importance in personalized medicine and has been revealed as a critical factor for discovery new disease variants. Here, we present Collaborative Spanish Variability Server (CSVS), which currently contains more than 2000 genomes exomes unrelated individuals. This database generated collaborative crowdsourcing effort collecting sequencing data produced by genomic projects other purposes. Sequences have grouped ICD10 upper...
Mutations in the ganglioside‐induced‐differentiation‐associated protein 1 gene ( GDAP1 ) can cause Charcot‐Marie‐Tooth (CMT) disease with demyelinating (CMT4A) or axonal forms (CMT2K and ARCMT2K). Most of these mutations present a recessive inheritance, but few autosomal dominant have also been reported. We performed screening clinically well‐characterized series 81 index cases CMT neuropathy, identifying 17 patients belonging to 4 unrelated families whom heterozygous p.R120W was found be...
We assessed the clinical outcome after coenzyme Q(10) (CoQ(10)) therapy in 14 patients presenting ataxia classified into two groups according to CoQ(10) values muscle (deficient or not). performed an open-label prospective study: were evaluated clinically (international cooperative rating scale [ICARS] scale, MRI, and videotape registration) at baseline every 6 months during a period of 2 years treatment (30 mg/kg/day). Patients with deficiency showed statistically significant reduction...
Mutations in SH3TC2 (KIAA1985) cause Charcot-Marie-Tooth disease (CMT) type 4C, a demyelinating inherited neuropathy characterized by early-onset and scoliosis. Here we demonstrate that the protein is present several components of endocytic pathway including early endosomes, late endosomes clathrin-coated vesicles close to trans-Golgi network plasma membrane. Myristoylation glycine 2 necessary but not sufficient for proper location cell membranes. In addition myristoylation, correct...
Mutations in the GDAP1 gene cause different forms of Charcot–Marie–Tooth (CMT) disease, and primary clinical expression this disease is markedly variable dominant inheritance form (CMT type 2K; CMT2K), which carriers p.R120W mutation can display a wide range severity. We investigated JPH1 as genetic modifier variability because junctophilin-1 (JPH1) good positional functional candidate. demonstrated that JPH1-GDAP1 cluster paralogon conserved vertebrates. Moreover, both proteins play role...
Mutations in SH3TC2 trigger autosomal recessive demyelinating Charcot-Marie-Tooth type 4C (CMT4C) neuropathy. Sh3tc2 is specifically expressed Schwann cells and necessary for proper myelination of peripheral axons. In line with the early onset neuropathy observed patients CMT4C, our analyses murine model CMT4C revealed that myelinating properties Sh3tc2-deficient are affected at an stage. This phenotype associated changes canonical Nrg1/ErbB pathway involved control myelination. We...
Mutations in MORC2 lead to an axonal form of Charcot-Marie-Tooth (CMT) neuropathy type 2Z. To date, 31 families have been described with mutations MORC2, indicating that this gene is frequently involved CMT cases. While the genetic data clearly establish causative role CMT2Z, impact its on neuronal biology and their phenotypic consequences patients remains be clarified. We show full-length highly expressed both embryonic adult human neural tissues Morc2 expression dynamically regulated...
Abstract The Ataxia Global Initiative (AGI) is a worldwide multi-stakeholder research platform to systematically enhance trial-readiness in degenerative ataxias. next-generation sequencing (NGS) working group of the AGI aims improve methods, platforms, and international standards for ataxia NGS analysis data sharing, ultimately allowing increase number genetically patients amenable natural history treatment trials. Despite extensive implementation clinical settings, diagnostic gap remains...
Four private mutations responsible for three forms demyelinating of Charcot-Marie-Tooth (CMT) or hereditary motor and sensory neuropathy (HMSN) have been associated with the Gypsy population: NDRG1 p.R148X in CMT type 4D (CMT4D/HMSN-Lom); p.C737_P738delinsX p.R1109X SH3TC2 gene (CMT4C); a G>C change novel alternative untranslated exon HK1 causative CMT4G (CMT4G/HMSN-Russe). Here we address findings genetic study 29 Spanish families autosomal recessive CMT. The most frequent form is CMT4C...