Extreme-Depth Re-sequencing of Mitochondrial DNA Finds No Evidence of Paternal Transmission in Humans.

Recent reports have questioned the accepted dogma that mammalian mitochondrial DNA (mtDNA) is strictly maternally inherited. In humans, the argument hinges on detecting a signature of inter-molecular recombination in mtDNA sequences sampled at the population level, inferring a paternal source for the mixed haplotypes. However, interpreting these data is fraught with difficulty, and direct experimental evidence is lacking.

Exome sequencing in undiagnosed inherited and sporadic ataxias.

Inherited ataxias are clinically and genetically heterogeneous, and a molecular diagnosis is not possible in most patients. Having excluded common sporadic, inherited and metabolic causes, we used an unbiased whole exome sequencing approach in 35 affected individuals, from 22 randomly selected families of white European descent. We defined the likely molecular diagnosis in 14 of 22 families (64%).

Use of whole-exome sequencing to determine the genetic basis of multiple mitochondrial respiratory chain complex deficiencies.

Importance: Mitochondrial disorders have emerged as a common cause of inherited disease, but their diagnosis remains challenging. Multiple respiratory chain complex defects are particularly difficult to diagnose at the molecular level because of the massive number of nuclear genes potentially involved in intramitochondrial protein synthesis, with many not yet linked to human disease.

Objective: To determine the molecular basis of multiple respiratory chain complex deficiencies.

Behr's Syndrome is Typically Associated with Disturbed Mitochondrial Translation and Mutations in the Gene.

Background: Behr's syndrome is a classical phenotypic description of childhood-onset optic atrophy combined with various neurological symptoms, including ophthalmoparesis, nystagmus, spastic paraparesis, ataxia, peripheral neuropathy and learning difficulties.

Objective: Here we describe 4 patients with the classical Behr's syndrome phenotype from 3 unrelated families who carry homozygous nonsense mutations in the gene encoding a protein involved in mitochondrial translation.

Methods: Whole exome sequencing was performed in genomic DNA and oxygen consumption was measured in patient cell lines.

Late-onset sacsinopathy diagnosed by exome sequencing and comparative genomic hybridization.

The molecular diagnosis of adult-onset autosomal recessive cerebellar ataxias remains challenging because of genetic heterogeneity. However, recently developed molecular genetic techniques will potentially revolutionize the diagnostic approach. Here we set out to define the genetic basis of the ataxia in two brothers with no molecular diagnosis.