Anita Elizabeth Harding was an Irish-British neurologist, and Professor of Clinical Neurology at the Institute of Neurology of the University of London. She is known for the discovery with Ian Holt and John Morgan-Hughes of the "first identification of a mitochondrial DNA mutation in human disease and the concept of tissue heteroplasmy of mutant mitochondrial DNA", published in Nature in 1986. In 1985 she established the first neurogenetics research group in the United Kingdom at the UCL Institute of Neurology.
Mitochondrial disease is a group of disorders caused by mitochondrial dysfunction. Mitochondria are the organelles that generate energy for the cell and are found in every cell of the human body except red blood cells. They convert the energy of food molecules into the ATP that powers most cell functions.
Leigh syndrome is an inherited neurometabolic disorder that affects the central nervous system. It is named after Archibald Denis Leigh, a British neuropsychiatrist who first described the condition in 1951. Normal levels of thiamine, thiamine monophosphate, and thiamine diphosphate are commonly found, but there is a reduced or absent level of thiamine triphosphate. This is thought to be caused by a blockage in the enzyme thiamine-diphosphate kinase, and therefore treatment in some patients would be to take thiamine triphosphate daily. While the majority of patients typically exhibit symptoms between the ages of 3 and 12 months, instances of adult onset have also been documented.
The Medical Research Council (MRC) is responsible for co-coordinating and funding medical research in the United Kingdom. It is part of United Kingdom Research and Innovation (UKRI), which came into operation 1 April 2018, and brings together the UK's seven research councils, Innovate UK and Research England. UK Research and Innovation is answerable to, although politically independent from, the Department for Business, Energy and Industrial Strategy.
Heteroplasmy is the presence of more than one type of organellar genome within a cell or individual. It is an important factor in considering the severity of mitochondrial diseases. Because most eukaryotic cells contain many hundreds of mitochondria with hundreds of copies of mitochondrial DNA, it is common for mutations to affect only some mitochondria, leaving most unaffected.
Homoplasmy is a term used in genetics to describe a eukaryotic cell whose copies of mitochondrial DNA are all identical. In normal and healthy tissues, all cells are homoplasmic. Homoplasmic mitochondrial DNA copies may be normal or mutated; however, most mutations are heteroplasmic. It has been discovered, though, that homoplasmic mitochondrial DNA mutations may be found in human tumors.
Leber's hereditary optic neuropathy (LHON) is a mitochondrially inherited degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; it predominantly affects young adult males. LHON is transmitted only through the mother, as it is primarily due to mutations in the mitochondrial genome, and only the egg contributes mitochondria to the embryo. Men cannot pass on the disease to their offspring. LHON is usually due to one of three pathogenic mitochondrial DNA (mtDNA) point mutations. These mutations are at nucleotide positions 11778 G to A, 3460 G to A and 14484 T to C, respectively in the ND4, ND1 and ND6 subunit genes of complex I of the oxidative phosphorylation chain in mitochondria.
Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of the family of mitochondrial diseases, which also include MIDD, MERRF syndrome, and Leber's hereditary optic neuropathy. It was first characterized under this name in 1984. A feature of these diseases is that they are caused by defects in the mitochondrial genome which is inherited purely from the female parent. The most common MELAS mutation is mitochondrial mutation, mtDNA, referred to as m.3243A>G.
MERRF syndrome is a mitochondrial disease. It is extremely rare, and has varying degrees of expressivity owing to heteroplasmy. MERRF syndrome affects different parts of the body, particularly the muscles and nervous system. The signs and symptoms of this disorder appear at an early age, generally childhood or adolescence. The causes of MERRF syndrome are difficult to determine, but because it is a mitochondrial disorder, it can be caused by the mutation of nuclear DNA or mitochondrial DNA. The classification of this disease varies from patient to patient, since many individuals do not fall into one specific disease category. The primary features displayed on a person with MERRF include myoclonus, seizures, cerebellar ataxia, myopathy, and ragged red fibers (RRF) on muscle biopsy, leading to the disease's name. Secondary features include dementia, optic atrophy, bilateral deafness, peripheral neuropathy, spasticity, or multiple lipomata. Mitochondrial disorders, including MERRFS, may present at any age.
The MRC Mitochondrial Biology Unit is a department of the School of Clinical Medicine at the University of Cambridge, funded through a strategic partnership between the Medical Research Council and the University. It is located at the Addenbrooke’s Hospital / Cambridge Biomedical Campus site in Cambridge, England. The unit is concerned with the study of the mitochondrion, as this organelle has a varied and critical role in many aspects of eukaryotic metabolism and is implicated in many metabolic, degenerative, and age-related human diseases.
MT-ND6 is a gene of the mitochondrial genome coding for the NADH-ubiquinone oxidoreductase chain 6 protein (ND6). The ND6 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Variations in the human MT-ND6 gene are associated with Leigh's syndrome, Leber's hereditary optic neuropathy (LHON) and dystonia.
Michael G Hanna is Director of the UCL Institute of Neurology, University College London and professor in clinical neurology and consultant neurologist at the National Hospital for Neurology and Neurosurgery, Queen Square, London, and also Director of the Medical Research Council (MRC) Centre for Neuromuscular Disease.
David Chaim Rubinsztein FRS FMedSci is the Deputy Director of the Cambridge Institute of Medical Research (CIMR), Professor of Molecular Neurogenetics at the University of Cambridge and a UK Dementia Research Institute Professor.
Sir Douglass Matthew Turnbull is Professor of Neurology at Newcastle University, an Honorary Consultant Neurologist at Newcastle upon Tyne Hospitals NHS Foundation Trust and a director of the Wellcome Trust Centre for Mitochondrial Research.
Mustafa Abdalla Mohamed Salih, , is a Sudanese academic professor, scientist and pediatric neurologist. He established the first pediatric neurology specialty in Sudan and is also one of the founders of the pediatric neurology specialty in Saudi Arabia. He identified inherited neurologic diseases which were subsequently named after him. Salih Myopathy, Salih ataxia, and Bosley-Salih-Alorainy syndrome resulting from mutations in HOXA1 gene. He is also known to have led a team of scientists who proved that the extract from broad beans also known as hoarse beans had the ability to cure epilepsy spasms. Mustafa is also credited for having discovered a novel form of hereditary spastic paraplegia.
Miratul Muqit FRSE FMedSci is a British neurologist and a Programme Lead at the MRC Protein Phosphorylation and Ubiquitylation Unit (MRCPPU) in the School of Life Sciences at the University of Dundee. His research focuses on the study of the PINK1 gene, mutations in which are a major cause of Parkinson's disease.
Martin Neil Rossor, is a British clinical neurologist with a specialty interest in degenerative dementias and familial disease.
Rita Horvath is a Hungarian neurologist and researcher. She completed her PhD on mitochondrial disease and research in Munich from 1999 to 2007.
Carolyn Mary Sue is an Australian physician-scientist, professor and research director. She has been the Executive Director of the Kolling Institute of Medical Research since 2019 and is also Director of Neurogenetics at Royal North Shore Hospital, Director of the Centre of Excellence for Parkinson's Disease and Movement Disorders, and Director of the National Centre for Adult Stem Cell Research. Sue specialises in complex neurogenetic conditions and runs tertiary referral clinics for patients with diseases such as Parkinson's, mitochondrial diseases, and other inherited movement disorders. Her research has identified several previously-unknown mutations that cause neurogenetic disease.
The Cambridge Institute for Medical Research (CIMR) is an interdisciplinary research institute within the University of Cambridge School of Clinical Medicine. CIMR is on the Cambridge Biomedical Campus, in the Keith Peters Building, a dedicated research building that it shares with the Medical Research Council Mitochondrial Biology Unit.
