- Ataxias and spastic paraparesis, emphasis on pathological nucleotide expansions
- Hereditary chorea and other hyperkinetic disorders
- Primary familial brain calcifications (PFBC)
Ataxias and spastic paraparesis, emphasis on pathological nucleotide expansions
Most pathological nucleotide expansions are associated with progressive and incurable neurodegenerative disorders. Ataxias and spastic paraparesis are in this context a continuum with significant clinical and molecular overlap. This project has an emphasis on establishing genotype-phenotype correlations, and searching for biomarkers for spinocerebellar ataxia 3, and FMR1-related disorders. Recent advances in genetics such as LRS has contributed to the discovery of the genetic basis for cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). CANVAS seems to be a common cause of familial ataxia in our patient population.
Researchers: Martin Paucar, Rula Zain-Luqman, José Laffita-Mesa, Daniel Nilsson, Per Svenningsson
Increasing involvement of CAPN1 variants in spastic ataxias and phenotype-genotype correlations. Jean-Loup Méreaux, Cristina Firanescu, Giulia Coarelli, Malin Kvarnung, Rita Rodrigues, Elena Pegoraro, Meriem Tazir, Frédéric Taithe, Rémi Valter, Vincent Huin, Kristina Lidström, Guillaume Banneau, Sara Morais, Livia Parodi, Marie Coutelier, Mélanie Papin, Per Svenningsson, Jean-Philippe Azulay, Isabel Alonso, Daniel Nilsson, Alexis Brice, Eric Le Guern, Rayomand Press, Giovanni Vazza, José Leal Loureiro, Cyril Goizet, Alexandra Durr, Martin Paucar, Giovanni Stevanin. Neurogenetics, January 2021
A novel duplication in ATXN2 as modifier for spinocerebellar ataxia 3 (SCA3/MJD) and C9ORF72-ALS. Laffita-Mesa J, Nennesmo I, Paucar M* and Svenningsson P*. Movement Disorders Sept 2020. * Equal contribution.
Broader phenotypic traits and widespread brain hypometabolism in spinocerebellar ataxia 27. Paucar M, Lundin J, Alshammari T, Bergendal Å, Lindefeldt M, Alshammari M, Solders G, Di Re J, Savitcheva I, Granberg T, Laezza F, Iwarsson E, Svenningsson P. J Intern Med. 202
Hereditary chorea and other hyperkinetic disorders
Huntington’s disease (HD) is the most common polyglutaminopahy and the most common form of familial chorea. The aim of this project is to search and validate biomarkers of HD. Part of this project is carried out in cooperation with researchers in Uppsala. Our work covers rare causes of familial chorea and hyperkinetic disorders.
Researchers: Martin Paucar, Per Svenningsson, Daniel Nilsson, Magnus Nordenskjöld
Proenkephalin decreases in cerebrospinal fluid with symptom progression of Huntington’s disease. Niemelä V, Landtblom AM, Nyholm D, Kneider M, Constantinescu R, Paucar M, Svenningsson P, Shevchenko G, Bergqvist J, Sundblom, J. Accepted in Movement Disorders, September 2020.
Heterozygous variants in DCC: beyond congenital mirror movements. Thams T, Islam M, Lindefeldt M, Nordgren A, Granberg T, Tesi B, Barbany G, Nilsson D, and Paucar M. Neurology Genetics, August 2020
Phenotypic variability in chorea- acanthocytosis associated with novel VPS13A mutations. Valter Niemelä, Ammar Salih, Daniela Solea, Björn Lindvall, Jan Weinberg, Tobias Granberg, Aikaterini Tzovla, Love Nordin, Torsten Danfors, Irina Savitcheva, Niklas Dahl, and Martin Paucar. Neurology Genetics, April 2020.
Novel Xp21.1 deletion associated with unusual features in a large McLeod syndrome kindred. Sveinsson O, Udd B, Svenningsson P, Gassner C, Engström C, Laffita-Mesa J, Solders G, Hertegård S, Savitcheva I, Jung HH, Tolnay M, Frey BM and Paucar M. Parkinsonism & Related Disorders. 2018; S1353-8020(18)30399-7.
Chorea, psychosis, acanthocytosis, and prolonged survival associated with ELAC2 mutations. Paucar M, Pajak A, Freyer C, Bergendal Å, Döry M, Laffita-Mesa JM, Stranneheim H, Lagerstedt-Robinson K, Savitcheva I, Walker RH, Wedell A, Wredenberg A, Svenningsson P. Neurology. 2018; 91(15):710-712.
Primary familial brain calcifications (PFBC)
PFBC are a growing group of rare genetic diseases with widely variable presentation. Our group has contributed to the discovery of mutations in PDGFB and a potential biomarker for the most common form of PFBC.
Researchers: Martin Paucar, Ingemar Björkhem, Håkan Almqvist, and Per Svenningsson
A SLC20A2 gene mutation carrier displaying ataxia and increased levels of cerebrospinal fluid phosphate. Paucar M, Almqvist H, Jelic V, Hagman G, Jörneskog G, Holmin, S, Björkhem I and Svenningsson, P. Journal of Neurological Sciences. 2017; 375:245-247.
Progressive brain calcifications and signs in a family with the L9R mutation in the PDGFB gene. Paucar M, Almqvist H, Saeed A, Bergendal G, Ygge J, Holmin S, Björkhem I, Svenningsson P. Neurology Genetics. 2016; 2(4).
PDGFB mutations cause brain calcifications in humans and mice. Keller A, Westenberger A, Sobrido MJ, García-Murias M, Domingo A, Sears RL, Lemos RR, Ordoñez-Ugalde A, Nicolas G, da Cunha JE, Rushing EJ, Hugelshofer M, Wurnig MC, Kaech A, Reimann R, Lohmann K, Dobričić V, Carracedo A, Petrović I, Miyasaki JM, Abakumova I, Mäe MA, Raschperger E, Zatz M, Zschiedrich K, Klepper J, Spiteri E, Prieto JM, Navas I, Preuss M, Dering C, Janković M, Paucar M, Svenningsson P, Saliminejad K, Khorshid HR, Novaković I, Aguzzi A, Boss A, Le Ber I, Defer G, Hannequin D, Kostić VS, Campion D, Geschwind DH, Coppola G, Betsholtz C, Klein C, Oliveira JR. Nature Genetics. 2013; 45(9):1077-82.