Mitochondrial Dysfunction and Calcium Dysregulation in Leigh Syndrome Induced Pluripotent Stem Cell Derived Neurons.

Leigh syndrome (LS) is the most frequent infantile mitochondrial disorder (MD) and is characterized by neurodegeneration and astrogliosis in the basal ganglia or the brain stem. At present, there is no cure or treatment for this disease, partly due to scarcity of LS models. Current models generally fail to recapitulate important traits of the disease.

The mutation m.13513G>A impairs cardiac function, favoring a neuroectoderm commitment, in a mutant-load dependent way.

Mitochondrial disorders (MDs) arise as a result of a respiratory chain dysfunction. While some MDs can affect a single organ, many involve several organs, the brain being the most affected, followed by heart and/or muscle. Many of these diseases are associated with heteroplasmic mutations in the mitochondrial DNA (mtDNA).

Establishment of a human DOA 'plus' iPSC line, IISHDOi003-A, with the mutation in the OPA1 gene: c.1635C>A; p.Ser545Arg.

We have generated a human iPSC line IISHDOi003-A from fibroblasts of a patient with a dominant optic atrophy 'plus' phenotype, harbouring a heterozygous mutation, c.1635C>A; p.Ser545Arg, in the OPA1 gene.

Generation of a human iPSC line from a patient with an optic atrophy 'plus' phenotype due to a mutation in the OPA1 gene.

Human iPSC line Oex2054SV.4 was generated from fibroblasts of a patient with an optic atrophy 'plus' phenotype associated with a heterozygous mutation in the OPA1 gene. Reprogramming factors OCT3/4, SOX2, CMYC and KLF4 were delivered using a non-integrative methodology that involves the use of Sendai virus.

Generation of a human iPSC line from a patient with a mitochondrial encephalopathy due to mutations in the GFM1 gene.

Human iPSC line GFM1SV.25 was generated from fibroblasts of a child with a severe mitochondrial encephalopathy associated with mutations in the GFM1 gene, encoding the mitochondrial translation elongation factor G1. Reprogramming factors OCT3/4, SOX2, CMYC and KLF4 were delivered using a non integrative methodology that involves the use of Sendai virus.