Severe mitochondrial encephalomyopathy caused by variants in gene.

Background: Mitochondria adjust their shape in response to the different energetic and metabolic requirements of the cell, through extremely dynamic fusion and fission events. Several highly conserved dynamin-like GTPases are involved in these processes and, among those, the OPA1 protein is a key player in the fusion of inner mitochondrial membranes. Hundreds of monoallelic or biallelic pathogenic gene variants have been described in , all associated with a plethora of clinical phenotypes without a straightforward genotype-phenotype correlation.

De Novo Mutation in a Patient with Encephalopathy, Cardiomyopathy and Fatal Non-Epileptic Paroxysmal Refractory Vomiting.

Mitochondrial fission and fusion are vital dynamic processes for mitochondrial quality control and for the maintenance of cellular respiration; they also play an important role in the formation and maintenance of cells with high energy demand including cardiomyocytes and neurons. The (dynamin-1 like) gene encodes for the DRP1 protein, an evolutionary conserved member of the dynamin family that is responsible for the fission of mitochondria; it is ubiquitous but highly expressed in the developing neonatal heart. De novo heterozygous pathogenic variants in the gene have been previously reported to be associated with neonatal or infantile-onset encephalopathy characterized by hypotonia, developmental delay and refractory epilepsy.

Systematic analysis of NDUFAF6 in complex I assembly and mitochondrial disease.

Isolated complex I (CI) deficiencies are a major cause of primary mitochondrial disease. A substantial proportion of CI deficiencies are believed to arise from defects in CI assembly factors (CIAFs) that are not part of the CI holoenzyme. The biochemistry of these CIAFs is poorly defined, making their role in CI assembly unclear, and confounding interpretation of potential disease-causing genetic variants.

Biallelic variants in GTPBP3: New patients, phenotypic spectrum, and outcome.

Introduction: COXPD23 is a rare mitochondrial disease caused by biallelic pathogenic variants in GTPBP3. We report on two siblings with a mild phenotype.

Case Reports: The young boy presented with global developmental delay, ataxic gait and upper limbs tremor, and the older sister with absence seizures and hypertrophic cardiomyopathy.

AFG3L2 Biallelic Mutation: Clinical Heterogeneity in Two Italian Patients.

AFG3-like matrix AAA peptidase subunit 2 gene (AFG3L2, OMIM * 604,581) biallelic mutations lead to autosomal recessive spastic ataxia-5 SPAX5, OMIM # 614,487), a rare hereditary form of ataxia. The clinical spectrum includes early-onset cerebellar ataxia, spasticity, and progressive myoclonic epilepsy (PME). In Italy, the epidemiology of the disease is probably underestimated.