Search

Mitochondrial disease is hugely diverse with respect to associated clinical presentations and underlying genetic causes, with pathogenic variants in over 300 disease genes currently described. Approximately half of these have been discovered in the last decade due to the increasingly widespread application of next generation sequencing technologies, in particular unbiased, whole exome—and latterly, whole genome sequencing. These technologies allow more genetic data to be collected from patients with mitochondrial disorders, continually improving the diagnostic success rate in a clinical setting. Despite these significant advances, some patients still remain without a definitive genetic diagnosis. Large datasets containing many variants of unknown significance have become a major challenge with next generation sequencing strategies and these require significant functional validation to confirm pathogenicity. This interface between diagnostics and research is critical in continuing to expand the list of known pathogenic variants and concomitantly enhance our knowledge of mitochondrial biology. The increasing use of whole exome sequencing, whole genome sequencing and other “omics” techniques such as transcriptomics and proteomics will generate even more data and allow further interrogation and validation of genetic causes, including those outside of coding regions. This will improve diagnostic yields still further and emphasizes the integral role that functional assessment of variant causality plays in this process—the overarching focus of this review.

Across a number of countries, play-based learning is the mandated pedagogy in early years’ curricula. However, a lack of consensus remains both in research and practice regarding the value and role of play in children's learning. This scoping review analyses 168 articles addressing play-based learning for 4–5 year old children divided into three categories: research on play for developmental learning, research on play for academic learning and factors influencing play in kindergarten classrooms. Much of the research endorsed play as fulfilling an important role in early learning. However, two disparate perspectives concerning the role of play for developmental versus academic learning demonstrate different orientations towards the value and potential benefits of play. Research focused on developmental learning endorsed the use of free play and a passive teacher role, while research focused on academic learning endorsed teacher-directed and mutually directed play where the teacher fulfills an active play role. A similar lack of consensus was found among research with educators regarding the role and benefits of play. These findings indicate a need to move away from a binary stance regarding play and towards an integration of perspectives and practices, with different types of play perceived as complementary rather than incompatible.

In Parkinson disease (PD), mitochondrial dysfunction associates with nigral dopaminergic neuronal loss. Cholinergic neuronal loss co-occurs, particularly within a brainstem structure, the pedunculopontine nucleus (PPN). We isolated single cholinergic neurons from postmortem PPNs of aged controls and PD patients. Mitochondrial DNA (mtDNA) copy number and mtDNA deletions were increased significantly in PD patients compared to controls. Furthermore, compared to controls the PD patients had significantly more PPN cholinergic neurons containing mtDNA deletion levels exceeding 60%, a level associated with deleterious effects on oxidative phosphorylation. The current results differ from studies reporting mtDNA depletion in nigral dopaminergic neurons of PD patients. Ann Neurol 2017;82:1016-1021.

BACKGROUND: Neurodegeneration with brain iron accumulation is clinically and genetically heterogeneous because of mutations in at least 7 nuclear genes. METHODS: We performed homozygosity mapping and whole-exome sequencing in 2 brothers with brain iron accumulation from a consanguineous family. RESULTS: We identified a homozygous missense mutation in both brothers in the very recently identified chromosome 19 open-reading frame 12 gene. The disease presented before age 10 with slowly progressive tremor, dystonia, and spasticity. Additional features were optic atrophy, peripheral neuropathy, and learning difficulties. A raised serum creatine kinase indicated neuromuscular involvement, and compensatory mitochondrial proliferation implicated mitochondrial dysfunction as a pathological mechanism. CONCLUSIONS: Further studies are needed to explore the function of the chromosome 19 open-reading frame 12 gene, and extended genetic analysis on larger patient cohorts will provide more information about the presentation and frequency of this disease.

This guide accompanies the following article: Pyle, A., DeLuca, C., & Danniels, E. (2017) A scoping review of research on play-based pedagogies in kindergarten education. Review of Education, https://doi.org/10.1002/rev3.3097