Dr Andrea Németh is a Clinician Scientist at the University of Oxford, and a Consultant in Neurogenetics at the Oxford University Hospitals NHS Trust. She trained at the Royal Free Hospital School of Medicine, and also undertook an intercalated BSc in Biochemistry and Neuropharmacology at the Royal Free and University College London. She then moved to Professor Kay Davies lab in Oxford as an MRC Clinical Training Fellow, completing her DPhil at the University of Oxford in 1995. Following this she was awarded a prestigous MRC Clinician Scientist Fellowship which she did at the Wellcome Trust Centre for Human Genetics in Oxford, and during this time developed her interest in ataxias, going on to characterise several novel genetic ataxia syndromes. Dr Nemeth completed her clinical training in Genetics while a Clinical Lecturer at the University of Oxford before becoming a Consultant in Neurogenetics and joining the NDCN.
Andrea H Németh
BSc; MB.BS; DPhil (Oxon); FRCP
Senior Clinical Research Fellow and Consultant in Neurogenetics
The main focus of my group is to understand the genetic mechanisms underlying normal function and disease within the central nervous system, including the retina and to use this information to help develop potential therapies for genetic conditions (Lufino et al., 2013). Our primary focus is on genetic mutations causing ataxias and retinal degeneration but also includes other conditions such as learning disability, dystonia and other movement disorders, epilepsy and spasticity.
Initially, we used positional cloning approaches to identifying novel genes associated with neurological disorders (Németh et al., 2000, Moreira et al., 2004) but this has been replaced with next generation sequencing (NGS) using targeted and exome capture in addition to whole genome sequencing (WGS).
We have developed NGS for clinical diagnostics in both retinal degeneration and ataxias and these tests have now been developed as NHS services through the Oxford Regional Molecular Genetics Laboratories (Shanks et al., 2012; Németh et al., 2013, Nature Reviews Neurology - view article here and Neurology Today - view article here).
We are now using these technologies to identify novel genes and genetic mechanisms causing neurogenetic disorders. In particular, we have funding from Action Medical Research and the Henry Smith Charity to investigate the genetic causes of ataxia in children.
We recently combined targeted capture with whole genome sequencing to identify a novel recessive ataxia, called SPARCA1 which is associated with mutations in SPTBN2 encoding BetaIII spectrin and is part of a group of disorders known as “neuronal spectrinopathies”. We are investigating the mechanisms underlying these conditions in collaboration with Dr Mandy Jackson and her team from the University of Edinburgh.
Our current interests include the development of bioinformatic algorithms and functional assays (Davies et al., 2012) to determine the pathogenicity of genetic variants and the development of whole genome sequencing for diagnostics and novel disease gene discovery.
Next generation sequencing for molecular diagnosis of neurological disorders using ataxias as a model.
Németh AH. et al, (2013), Brain, 136, 3106 - 3118
Recessive mutations in SPTBN2 implicate β-III spectrin in both cognitive and motor development.
Lise S. et al, (2012), PLoS Genet, 8
Autosomal recessive cerebellar ataxia with oculomotor apraxia (ataxia-telangiectasia-like syndrome) is linked to chromosome 9q34.
Németh AH. et al, (2000), Am J Hum Genet, 67, 1320 - 1326
Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2.
Moreira MC. et al, (2004), Nat Genet, 36, 225 - 227
A GAA repeat expansion reporter model of Friedreich's ataxia recapitulates the genomic context and allows rapid screening of therapeutic compounds.
Lufino MM. et al, (2013), Hum Mol Genet, 22, 5173 - 5187
De Novo Mutations in EBF3 Cause a Neurodevelopmental Syndrome.
Sleven H. et al, (2017), Am J Hum Genet, 100, 138 - 150
Clinical features of the pathogenic m.5540G>A mitochondrial transfer RNA tryptophan gene mutation.
Ng YS. et al, (2016), Neuromuscul Disord, 26, 702 - 705
Genetic testing in neurology
Lefroy H. et al, (2016), Medicine (United Kingdom), 44, 508 - 512
A Restricted Repertoire of De Novo Mutations in ITPR1 Cause Gillespie Syndrome with Evidence for Dominant-Negative Effect.
McEntagart M. et al, (2016), Am J Hum Genet, 98, 981 - 992
Whole Genome Sequencing Increases Molecular Diagnostic Yield Compared with Current Diagnostic Testing for Inherited Retinal Disease.
Ellingford JM. et al, (2016), Ophthalmology, 123, 1143 - 1150