I studied medicine at the Semmelweis Medical School in Budapest. As I was passionate about combining clinical work and research, I started my career as a Clinical Research Fellow at the Hungarian Academy of Sciences. I received funding from the Soros Foundation to do research in mitochondrial diseases with Professor Eric Shoubridge in the Montreal Neurological Institute, which determined the direction of my career ever since. After my return to Budapest, I introduced genetic testing for mitochondrial disease in Hungary, completed my PhD on mitochondrial encephalomyopathies and became a consultant in neurology.
I moved to Munich, Germany in 1999 and started research in mitochondrial diseases in a laboratory associated to a clinical service and to the university in Munich. I subsequently moved to the MGZ Munich and established a new mitochondrial genetic diagnostic service.
In 2007 I moved to the UK to take up the position of Lecturer in Mitochondrial Disease at Newcastle University, and was promoted to Senior Lecturer in 2010. I successfully developed my own research and secured research funding in the UK. As a clinician I have established a new service in Newcastle for patients with inherited peripheral nerve disease (Charcot-Marie-Tooth disease, CMT), which can be a basis of future research.
I started my research career in 1995 focusing on clinical characterisation of mitochondrial diseases (such as Leber’s hereditary optic neuropathy). In 2000-2007 my research was based on a diagnostic service in Munich, and I focused on identifying the primary cause in a high number of patients with different types of mitochondrial disease, but also to study basic disease mechanisms. Based on my diagnostic experience in Germany I was able to define the phenotype of a group of patients, small children exhibiting severe mitochondrial disease due to mitochondrial translation defects or coenzyme Q10 deficiencies, which has become my research area more recently.
The main focus of my research is to identify the molecular basis of disease and to develop treatments for patients with mitochondrial encephalomyopathies. The underlying genetic defect in many of these patients remains unknown and there are no effective treatments. One direction of my research is to study a large group of children with severe mitochondrial disease to identify novel disease genes. I have recently received funding for studying a unique mitochondrial condition: reversibe infantile cytochrome c oxidase (COX) deficiency. Most mitochondrial diseases are progressive conditions however this syndrome stands out by showing spontaneous recovery. Finding a clearly pathogenic homoplasmic mtDNA mutation in this reversible mitochondrial disease offers a new paradigm of mtDNA pathogenesis. My research focuses on studying this unique disease to unveil factors that are important in other mitochondrial disease. A better understanding of the compensatory factors will offer important clues towards molecular therapies.
As a clinican, I have started and developed a new clinical service over the last 3 years in Newcastle for a large group of patients with inherited peripheral neuropathies (Charcot-Marie-Tooth disease, CMT). The better characterisation of the clinical phenotypes, the improvement of next generation sequencing techniques enables us to identify the primary genetic cause in a much higher number of patients with CMT. This patient cohort will be a base for expanding my research activities and the base of further grant applications to start a new area of research in Newcastle.
Rita’s research project is listed below. Click on the link to learn more.
- Studying the underlying cause and molecular mechanisms of childhood-onset combined respiratory chain deficiencies.
Recently I received substantial funding from the European Research Council (ERC) to study basic mechanisms of mitochondrial translation.
Awards, honours and professional service
1988 M.D. Semmelweis Medical University, Budapest, Hungary
1992 neurology Semmelweis Medical University, Budapest, Hungary
1995 Soros Foundation, fellowship, Montreal Neurological Institute, Montreal, Canada
2000 PhD Hungarian Academy of Sciences
2006 Felix-Jerusalem Prize for outstanding research in muscle disease, Germany
Recent Key Publications
Boczonadi V, Müller V, Pyle A, Munkley J, Dor T, Quartararo J, Ferrero I, Karcagi V, Giunta M, Polvikoski T, Birchall D, Princzinger A, Cinnamon Y, Lützkendorf S, Piko H, Reza M, Florez L, Santibanez-Koref M, Griffin H, Schuelke M, Elpeleg O, Kalaydjieva L, Lochmüller H, Elliott DJ, Chinnery PF, Edvardson S and Horvath R. EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia. Nat. Commun. 2014;5:4287.
Taylor RW, Pyle A, Griffin H, Blakely EL, Duff J, He L, Smertenko T, Alston CL, Neeve VC, Best A, Yarham JW, Kirschner J, Schara U, Talim B, Topaloglu H, Baric I, Holinski-Feder E, Abicht A, Czermin B, Kleinle S, Morris AAM, Vassallo G, Gorman GS, Turnbull DM, Ramesh V, Santibanez-Koref M, McFarland R, Horvath R* (joint last author), Chinnery PF*. Whole exome sequencing defines the genetic basis of multiple mitochondrial respiratory chain complex deficiency. JAMA 2014;312:68-77.
Hermann DN*, Horvath R* (joint first author), Sowden JE, Guan Z, Whittaker RG, Almodovar JL, Lane M, Bansagi B, Pyle A, Boczonadi V, Lochmüller H, Griffin H, Chinnery PF, Gonzales M, Sanchez-Mejias A, Lloyd TE, Littleton JT, Zuchner S. Mutations in Synaptotagmin 2 cause an autosomal dominant form of Lambert-Eaton myasthenic syndrome and non-progressive motor neuropathy. Am. J. Hum. Genet. 2014;95:332-339.
Boczonadi V, Smith PM, Pyle A, Gomez-Duran A, Schara U, Tulinius M, Chinnery PF, Horvath R. Altered 2-thiouridylation impairs mitochondrial translation in reversible infantile respiratory chain deficiency. Hum. Mol. Genet. 2013;22:4602-4615.
Neeve VCM, Samuels DC, Bindoff LA, van den Bosch B, Van Goethem G, Smeets H, Lombès A, Jardel C, Hirano M, DiMauro S, De Vries M, Smeitink J, Smits B, de Coo IFM, Saft C, Klopstock T, Keiling BC, Czermin B, Abicht A, Lochmüller H, Hudson G, Gorman GG, Turnbull DM, Taylor RW, Holinski-Feder E, Chinnery PF, Horvath R. What is influencing the phenotype of the common homozygous polymerase g mutation p.Ala467Thr? Brain 2012;135:3614-3626.
Kemp JP, Smith PM, Pyle A, Neeve VCM, Tuppen HAL, Schara U, Talim B, Topaloglu H, Holinski-Feder E, Abicht A, Czermin B, Lochmüller H, McFarland R, Chinnery PF, Chrzanowska-Lightowlers ZMA, Lightowlers RN, Taylor RW, Horvath R. Nuclear factors involved in mitochondrial translation cause a subgroup of combined respiratory chain deficiency Brain 2011;134:183-195.
Horvath R, Kemp JP, Tuppen HAL, Hudson G, Oldfors A, Marie SKN, Moslemi A-R, Servidei S, Holme E, Shanske S, Kollberg G, Jayakar P, Pyle A, Marks HM, Holinski-Feder E, Scavina M, Walter MC, Çoku J, Günther-Scholz A, Smith PM, McFarland R, Chrzanowska-Lightowlers ZMA, Lightowlers RN, Hirano M, Lochmüller H, Taylor RW, Chinnery PF, Tulinius M, DiMauro S. Molecular basis of infantile reversible COX deficiency myopathy, Brain 2009;132:3165-3174.
Bulst S, Abicht A, Holinski-Feder E, Müller-Ziermann S, Koehler U, Thirion C, Walter MC, Stewart JD, Chinnery PF, Lochmüller H, Horvath R. In vitro supplementation with dAMP/dGMP leads to partial restoration of mtDNA levels in mitochondrial depletion syndromes. Hum. Mol. Genet. 2009;18:1590-1599.
Weraarpachai W, Antonicka H, Sasarman F, Seeger J, Schrank B, Kolesar JE, Lochmüller H, Chevrette M, Kaufman BA, Horvath R, Shoubridge EA. Mutation in TACO1, encoding a translational activator of COX I, results in cytochrome c oxidase deficiency and late-onset Leigh syndrome. Nat. Genet. 2009;41:833-837.
Ghezzi D, Goffrini P, Uziel G, Horvath R, Klopstock T, Lochmüller H, D’Adamo P, Gasparini P, Strom TM, Prokisch H, Invernizzi F, Ferrero I, Zeviani M. SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy. Nat. Genet. 2009;41:654-656.
2016. Novel genetic and neuropathological insights in NARP.  Muscle Nerve.,
2016. Both mitochondrial DNA and mitonuclear gene mutations cause hearing loss through cochlear dysfunction.  Brain 139(Pt 6):e33,
2016. Erratum to: The neurological and ophthalmological manifestations of SPG4-related hereditary spastic paraplegia.  J Neurol 263(2):419-20,
2016. Amyloid-β in mitochondrial disease: mutation in a human metallopeptidase links amyloidotic neurodegeneration with mitochondrial processing.  EMBO Mol Med 8(3):173-5,
2016. Riboflavin-Responsive and -Non-responsive Mutations in FAD Synthase Cause Multiple Acyl-CoA Dehydrogenase and Combined Respiratory-Chain Deficiency.  Am J Hum Genet 98(6):1130-45,
2016. Mitochondrial dysfunction in liver failure requiring transplantation.  J Inherit Metab Dis 39(3):427-36,
2016. Mitochondrial DNA sequence characteristics modulate the size of the genetic bottleneck.  Hum Mol Genet 25(5):1031-41,
2016. Altered RNA metabolism due to a homozygous RBM7 mutation in a patient with spinal motor neuropathy.  Hum Mol Genet.,
2016. Can aliphatic anchoring groups be utilised with dyes for p-type dye sensitized solar cells?  Dalton Trans 45(18):7708-19,
2016. Emerging therapies for mitochondrial disorders.  Brain 139(Pt 6):1633-48,
2016. Homozygous deletion in MICU1 presenting with fatigue and lethargy in childhood.  Neurol Genet 2(2):e59,
2015. Reply: Evaluation of exome sequencing variation in undiagnosed ataxias.  Brain 138(Pt 10):e384,
2015. SPG7 mutations are a common cause of undiagnosed ataxia.  Neurology 84(11):1174-6,
2015. Modifying mitochondrial tRNAs: delivering what the cell needs.  Cell Metab 21(3):351-2,
2015. Investigating the role of the physiological isoform switch of cytochrome c oxidase subunits in reversible mitochondrial disease.  Int J Biochem Cell Biol 63:32-40,
2015. Clinical heterogeneity of primary familial brain calcification due to a novel mutation in PDGFB.  Neurology 84(17):1818-20,
2015. Exome sequencing in undiagnosed inherited and sporadic ataxias.  Brain 138(Pt 2):276-83,
2015. Phenotypic variability of TRPV4 related neuropathies.  Neuromuscul Disord 25(6):516-21,
2015. Use of stereotypical mutational motifs to define resolution limits for the ultra-deep resequencing of mitochondrial DNA.  Eur J Hum Genet 23(3):413-5,
2015. Reversible infantile mitochondrial diseases.  J Inherit Metab Dis 38(3):427-35,
2015. A novel de novo STXBP1 mutation is associated with mitochondrial complex I deficiency and late-onset juvenile-onset parkinsonism.  Neurogenetics 16(1):65-7,
2015. Exosomal Protein Deficiencies: How Abnormal RNA Metabolism Results in Childhood-Onset Neurological Diseases.  J Neuromuscul Dis 2(Suppl 2):S31-S37,
2015. Clonal expansion of secondary mitochondrial DNA deletions associated with spinocerebellar ataxia type 28.  JAMA Neurol 72(1):106-11,
2015. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease.  Ann Neurol 77(5):753-9,
2015. Frequency of rare recessive mutations in unexplained late onset cerebellar ataxia.  J Neurol 262(8):1822-7,
2015. Whole exome sequencing and the clinician: we need clinical skills and functional validation in variant filtering.  J Neurol 262(7):1673-7,
2015. SCP2 mutations and neurodegeneration with brain iron accumulation.  Neurology 85(21):1909-11,
2015. Electrophysiologic features of SYT2 mutations causing a treatable neuromuscular syndrome.  Neurology 85(22):1964-71,
2015. ATP synthase deficiency due to TMEM70 mutation leads to ultrastructural mitochondrial degeneration and is amenable to treatment.  Biomed Res Int 2015:462592,
2015. Respiratory chain deficiency in nonmitochondrial disease.  Neurol Genet 1(1):e6,
2015. Mitochondrial pathology in progressive cerebellar ataxia.  Cerebellum Ataxias 2:16,
2015. Prevalence of neurogenetic disorders in the North of England.  Neurology 85(14):1195-201,
2015. Epilepsy in adults with mitochondrial disease: A cohort study.  Ann Neurol 78(6):949-57,
2015. Nuclear-mitochondrial proteins: too much to process?  Brain 138(Pt 6):1451-3,
2015. Clinical and pathological features of mitochondrial DNA deletion disease following antiretroviral treatment.  JAMA Neurol 72(5):603-5,
2015. The p.Ser107Leu in BICD2 is a mutation 'hot spot' causing distal spinal muscular atrophy.  Brain 138(Pt 11):e391,
2015. Genotype/phenotype correlations in AARS-related neuropathy in a cohort of patients from the United Kingdom and Ireland.  J Neurol 262(8):1899-908,
2015. Early-onset leukoencephalopathy due to a homozygous missense mutation in the DARS2 gene.  Mol Cell Probes 29(5):319-22,
2015. Voxel-based analysis in neuroferritinopathy expands the phenotype and determines radiological correlates of disease severity.  J Neurol 262(10):2232-40,
2014. Abnormal retinal thickening is a common feature among patients with ARSACS-related phenotypes.  Br J Ophthalmol 98(5):711-3,
2014. Chronic and slowly progressive weakness of the legs and hands.  BMJ 348:g459,
2014. Mitochondria: impaired mitochondrial translation in human disease.  Int J Biochem Cell Biol 48:77-84,
2014. Titin founder mutation is a common cause of myofibrillar myopathy with early respiratory failure.  J Neurol Neurosurg Psychiatry 85(3):331-8,
2014. An under-recognised cause of spastic paraparesis in middle-aged women.  Pract Neurol 14(3):182-4,
2014. Reply: Hereditary myopathy with early respiratory failure is caused by mutations in the titin FN3 119 domain.  Brain 137(Pt 4):e271,
2014. Behr's Syndrome is Typically Associated with Disturbed Mitochondrial Translation and Mutations in the C12orf65 Gene.  J Neuromuscul Dis 1(1):55-63,
2014. Mutations in the Mitochondrial Citrate Carrier SLC25A1 are Associated with Impaired Neuromuscular Transmission.  J Neuromuscul Dis 1(1):75-90,
2014. Two recurrent mutations are associated with GNE myopathy in the North of Britain.  J Neurol Neurosurg Psychiatry 85(12):1359-65,
2014. Valproic acid triggers increased mitochondrial biogenesis in POLG-deficient fibroblasts.  Mol Genet Metab 112(1):57-63,
2014. Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy.  Am J Hum Genet 95(3):332-9,
2014. Truncating and missense mutations in IGHMBP2 cause Charcot-Marie Tooth disease type 2.  Am J Hum Genet 95(5):590-601,
2014. Founder p.Arg 446* mutation in the PDHX gene explains over half of cases with congenital lactic acidosis in Roma children.  Mol Genet Metab 113(1-2):76-83,
2014. Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance.  Brain 137(Pt 5):1323-36,
2014. Accurate mitochondrial DNA sequencing using off-target reads provides a single test to identify pathogenic point mutations.  Genet Med 16(12):962-71,
2013. Brain iron takes off: a new propeller protein links neurodegeneration with autophagy.  Brain 136(Pt 6):1687-91,
2013. Clinical and functional characterisation of the combined respiratory chain defect in two sisters due to autosomal recessive mutations in MTFMT.  Mitochondrion 13(6):743-8,
2013. Universal heteroplasmy of human mitochondrial DNA.  Hum Mol Genet 22(2):384-90,
2013. Altered 2-thiouridylation impairs mitochondrial translation in reversible infantile respiratory chain deficiency.  Hum Mol Genet 22(22):4602-15,
2013. Initial development and validation of a mitochondrial disease quality of life scale.  Neuromuscul Disord 23(4):324-9,
2013. Extending the KCNQ2 encephalopathy spectrum: clinical and neuroimaging findings in 17 patients.  Neurology 81(19):1697-703,
2013. New treatments for mitochondrial disease-no time to drop our standards.  Nat Rev Neurol 9(8):474-81,
2013. Late-onset respiratory failure due to TK2 mutations causing multiple mtDNA deletions.  Neurology 81(23):2051-3,
2013. Fibroblast growth factor 21, a biomarker for mitochondrial muscle disease.  Neurology 81(21):1808-9,
2013. Late-onset sacsinopathy diagnosed by exome sequencing and comparative genomic hybridization.  J Neurogenet 27(4):176-82,
2013. Near-identical segregation of mtDNA heteroplasmy in blood, muscle, urinary epithelium, and hair follicles in twins with optic atrophy, ptosis, and intractable epilepsy.  JAMA Neurol 70(12):1552-5,
2013. Mitochondrial DNA deletions in muscle satellite cells: implications for therapies.  Hum Mol Genet 22(23):4739-47,
2012. A new phenotype of brain iron accumulation with dystonia, optic atrophy, and peripheral neuropathy.  Mov Disord 27(6):789-93,
2012. Update on clinical aspects and treatment of selected vitamin-responsive disorders II (riboflavin and CoQ 10).  J Inherit Metab Dis 35(4):679-87,
2012. Adult-onset cerebellar ataxia due to mutations in CABC1/ADCK3.  J Neurol Neurosurg Psychiatry 83(2):174-8,
2012. Genetic variations within the OPA1 gene are not associated with neuromyelitis optica.  Mult Scler 18(2):240-3,
2012. Titin mutation segregates with hereditary myopathy with early respiratory failure.  Brain 135(Pt 6):1695-713,
2012. What is influencing the phenotype of the common homozygous polymerase-γ mutation p.Ala467Thr?  Brain 135(Pt 12):3614-26,
2012. OPA1 mutations induce mtDNA proliferation in leukocytes of patients with dominant optic atrophy.  Neurology 79(14):1515-7,
2012. Adult-onset spinocerebellar ataxia syndromes due to MTATP6 mutations.  J Neurol Neurosurg Psychiatry 83(9):883-6,
2012. Prominent sensorimotor neuropathy due to SACS mutations revealed by whole-exome sequencing.  Arch Neurol 69(10):1351-4,
2011. POLG mutations cause decreased mitochondrial DNA repopulation rates following induced depletion in human fibroblasts.  Biochim Biophys Acta 1812(3):321-5,
2011. 175th ENMC International Workshop: Mitochondrial protein synthesis in health and disease, 25-27th June 2010, Naarden, The Netherlands.  Neuromuscul Disord 21(2):142-7,
2011. Nuclear factors involved in mitochondrial translation cause a subgroup of combined respiratory chain deficiency.  Brain 134(Pt 1):183-95,
2011. Variation in MAPT is not a contributing factor to the incomplete penetrance in LHON.  Mitochondrion 11(4):620-2,
2011. Recurrent stroke-like episodes in X-linked Charcot-Marie-Tooth disease.  Neurology 77(12):1205-6,
2011. An unusual gait following the discovery of a new disease.  Pract Neurol 11(2):81-4,
2011. Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations.  Nat Genet 43(8):806-10,
2010. Multi-system neurological disease is common in patients with OPA1 mutations.  Brain 133(Pt 3):771-86,
2010. The prevalence and natural history of dominant optic atrophy due to OPA1 mutations.  Ophthalmology 117(8):1538-46, 1546.e1,
2010. A novel mitochondrial MTND5 frameshift mutation causing isolated complex I deficiency, renal failure and myopathy.  Neuromuscul Disord 20(2):131-5,
2010. Mitochondrial myopathies: developments in treatment.  Curr Opin Neurol 23(5):459-65,
2010. The pathogenic m.3243A>T mitochondrial DNA mutation is associated with a variable neurological phenotype.  Neuromuscul Disord 20(6):403-6,
2010. Polymerase γ gene POLG determines the risk of sodium valproate-induced liver toxicity.  Hepatology 52(5):1791-6,
2010. Long-term survival of neonatal mitochondrial complex III deficiency associated with a novel BCS1L gene mutation.  Mol Genet Metab 100(4):345-8,
2009. Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy.  Brain 132(Pt 11):3165-74,
2008. How can we treat mitochondrial encephalomyopathies? Approaches to therapy.  Neurotherapeutics 5(4):558-68,
2008. OPA1 in multiple mitochondrial DNA deletion disorders.  Neurology 71(22):1829-31,
2007. X-Inactivation patterns in females harboring mtDNA mutations that cause Leber hereditary optic neuropathy.  Mol Vis 13:2339-43,
2007. Clinical expression of Leber hereditary optic neuropathy is affected by the mitochondrial DNA-haplogroup background.  Am J Hum Genet 81(2):228-33,
2005. Identification of an X-chromosomal locus and haplotype modulating the phenotype of a mitochondrial DNA disorder.  Am J Hum Genet 77(6):1086-91,
2004. Risk of developing a mitochondrial DNA deletion disorder.  Lancet 364(9434):592-6,