The Clinical Neurogenetics Unit research program is focused on identification and characterization of genes and genetic mechanisms involved in hereditary a) movement disorders, b) neuromuscular disorders, and c) prion diseases. Major findings: A clinically and pathologically distinct type of cardioskeletal myopathy is associated with mutations in the desmin gene: eleven novel causative mutations have now been identified and described, and adverse effects of each mutation tested in a cell culture expression system. An extremely aggressive variant of malignant hyperthermia was characterized in large North and South American families. It was linked to a novel mutation in the ryanodine receptor (RYR1) gene. A new study shows that worldwide distribution of hereditary Creutzfeldt-Jakob disease/Fatal Insomnia associated with the PRNP D178N mutation depends on recurrent mutations rather than founder effect. Genetic susceptibility to kuru and new variant Creutzfeldt-Jakob disease is tightly linked to a M/V polymorphism in the PRNP gene. Based on these data, a model have been developed that helps to determine the dynamics of the nvCJD epidemic in the UK and predict its outcome.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Intramural Research (Z01)
Project #
1Z01NS002973-03
Application #
6548727
Study Section
(OCD)
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2001
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Platonov, Fedor A; Tyryshkin, Kathrin; Tikhonov, Dmitriy G et al. (2016) Genetic fitness and selection intensity in a population affected with high-incidence spinocerebellar ataxia type 1. Neurogenetics 17:179-85
Goldfarb, Lev G; Dalakas, Marinos C (2009) Tragedy in a heartbeat: malfunctioning desmin causes skeletal and cardiac muscle disease. J Clin Invest 119:1806-13
Dalakas, Marinos C; Rakocevic, Goran; Shatunov, Alexey et al. (2007) Inclusion body myositis with human immunodeficiency virus infection: four cases with clonal expansion of viral-specific T cells. Ann Neurol 61:466-75
Pruszczyk, Piotr; Kostera-Pruszczyk, Anna; Shatunov, Alexey et al. (2007) Restrictive cardiomyopathy with atrioventricular conduction block resulting from a desmin mutation. Int J Cardiol 117:244-53
Vladimirtsev, Vsevolod A; Nikitina, Raisa S; Renwick, Neil et al. (2007) Family clustering of Viliuisk encephalomyelitis in traditional and new geographic regions. Emerg Infect Dis 13:1321-6
Salajegheh, M; Rakocevic, G; Raju, R et al. (2007) T cell receptor profiling in muscle and blood lymphocytes in sporadic inclusion body myositis. Neurology 69:1672-9
Olive, Montse; Armstrong, Judith; Miralles, Francesc et al. (2007) Phenotypic patterns of desminopathy associated with three novel mutations in the desmin gene. Neuromuscul Disord 17:443-50
Kostera-Pruszczyk, Anna; Pruszczyk, Piotr; Kaminska, Anna et al. (2007) Diversity of cardiomyopathy phenotypes caused by mutations in desmin. Int J Cardiol :
Bar, Harald; Goudeau, Bertrand; Walde, Sarah et al. (2007) Conspicuous involvement of desmin tail mutations in diverse cardiac and skeletal myopathies. Hum Mutat 28:374-86
Shatunov, Alexey; Sambuughin, Nyamkhishig; Jankovic, Joseph et al. (2006) Genomewide scans in North American families reveal genetic linkage of essential tremor to a region on chromosome 6p23. Brain 129:2318-31

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