Patrick F Chinnery

..These observations open the door to future studies investigating the role of mtDNA methylation in human disease...

..Our findings suggest that genetic variation in MAPT is unlikely to make a major contribution to the risk of blindness among LHON mutation carriers...

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..The authors report two families with onset of ataxia in adulthood (with pyramidal dysfunction and/or peripheral neuropathy variably present), who are clinically indistinguishable from other spinocerebellar ataxia patients...

..The exclusive detection of m.14484T-->C on haplogroup J implicates the background mtDNA haplotype in mutagenesis. These findings emphasize the importance of developing new approaches to prevent transmission...

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..Our results suggest that the mitochondrial DNA background plays an important role in modifying the disease phenotype but nuclear modifiers, epigenetic and environmental factors may also influence the severity of disease...

..To define the prevalence and natural history of this optic nerve disorder, we performed a population-based epidemiologic and molecular study of presumed DOA cases in the north of England...

..Inherited ataxias are heterogeneous disorders affecting both children and adults. The primary cause can be identified in about half of the patients and only very few can receive causative therapy...

..We therefore screened for OPA1 in 32 patients with NMO. No pathogenic mutations were found, and none of the 13 single-nucleotide polymorphisms identified were associated with an increased risk of developing NMO...

..This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis...

..Ostensibly de novo somatic mtDNA mutations, seen in mtDNA maintenance disorders and neurodegenerative disease and aging, will partly be due to the clonal expansion of low-level inherited variants...

..Neurodegeneration with brain iron accumulation is clinically and genetically heterogeneous because of mutations in at least 7 nuclear genes...

..Small studies have failed to detect dramatic skewed X-inactivation in women transmitting LHON mutations. However, segregation analyses predicted skewing only in a proportion of women, which would not have been detected in these studies...

..Folate deficiency is known to cause bilateral optic neuropathy, and defects of folate metabolism have been associated with nonarteritic ischemic optic neuropathy...

..To determine the genetic basis of an unexplained multisystem neurological disorder affecting 2 siblings...

..With 363 exons, screening TTN presented a major challenge until recently. However, whole exome sequencing provides a reliable cost-effective approach, providing the gene of interest is adequately captured...

..This conclusion has important implications for prevention of mtDNA disease and, potentially, for our understanding of the aging process...

..There are currently limited treatments for these blinding ocular disorders and, ultimately, the aim is to translate these major advances into tangible benefits for patients and their families...

..We investigated whether there is an association between mtDNA haplotypes and incidence of stroke...

..Here we review current understanding of the factors regulating the amount of mtDNA within cells and discuss the relevance of these findings to our understanding of the inheritance of mtDNA heteroplasmy...

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..Initial studies implicate maternally inherited variants of mitochondrial DNA (mtDNA) in subgroups of patients with OA based on gender and specific joint involvement, but these findings have not been replicated...

..Random population sampling of ~10% of the extant herd identified a single mtDNA haplotype harbouring a unique bovine variant present in all other higher mammals (m.11789C/Y421H) which may contribute to their survival...

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..CONCLUSION: These findings implicate impaired liver regeneration in VPA toxicity and show that prospective genetic testing of POLG will identify individuals at high risk of this potentially fatal consequence of treatment...

..These observations add weight to the role of somatic mtDNA mutations in the aging process and raise the specter of progressive iatrogenic mitochondrial genetic disease emerging over the next decade...

..The ultimate goal is to translate these research advances into clinical practice and new treatment strategies are currently being investigated to improve the visual prognosis for patients with mitochondrial optic neuropathies...

..3243A>G. The early detection of cardiac dysfunction with MRI opens up opportunities to prevent heart failure in these patients through early intervention...

..We have investigated the cellular basis of the mtDNA depletion in sepsis, and determined clinical correlates with mtDNA depletion...

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..This major update was carried out to identify new studies and grade the original studies for potential bias in accordance with revised Cochrane Collaboration guidelines...

..This demonstrates the importance of OPA1 in mtDNA maintenance, and implicates OPA1 in diseases associated with secondary defects of mtDNA...

..The study also illustrates the immense diagnostic progress since the first regional survey over 50 years ago by Walton and Nattrass...

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..Substitutions on MTCYB provide an explanation for these findings, which demonstrate that common genetic variants have a marked effect on the expression of an ostensibly monogenic mtDNA disorder...

..Emphasis is placed on practical management considerations while including some recent updates in the field...

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..This approach will help to accelerate the identification of new mitochondrial disease genes by providing a principled way for the selection for combination of appropriate prediction methods of mitochondrial localization of proteins...

..The results indicate that mutation in GBA leads to additional lysosomal abnormalities, enhanced by an impaired UPR, potentially causing α-synuclein accumulation...

..Existing therapies continue to be evaluated and novel treatment strategies are starting to appear on the horizon...

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..All three harbouring the pathogenic c.460InsA mutation showed iron deposition; these findings show pathological iron accumulation begins in early childhood which is of major importance in understanding and developing treatment for NBIA...

..Herein, we summarize current concepts of NBIA pathogenesis and discuss important gaps in current knowledge, outlining key questions in the field...

..These findings demonstrate phenotypic overlap between SCA6 and episodic ataxia type 2, which are both due to mutations in CACNL1A4...

..The work confirms the involvement of the cerebellum in verbal working memory and defines specific subsystems for this within the cerebellum...