Molecular Diagnosis of Neurogenetic Disorders: General Issues, Huntington's Disease, Parkinson's Disease and Dystonias
H. F. Harbo
Oslo University Hospital, and University of Oslo, Oslo, Norway
Search for more papers by this authorJ. Finsterer
Rudolfstiftung and Danube University, Krems, Vienna, Austria
Search for more papers by this authorJ. Baets
University Hospital of Antwerp, Antwerp, Belgium
Institute Born-Bunge and University of Antwerp, Antwerp, Belgium
Search for more papers by this authorC. Van Broeckhoven
Institute Born-Bunge and University of Antwerp, Antwerp, Belgium
Search for more papers by this authorS. Di Donato
IRCCS Foundation Neurological Institute Carlo Besta, Milan, Italy
Search for more papers by this authorB. Fontaine
Assistance Publique-Hôpitaux de Paris, Centre de référence des canalopathies musculaires, Groupe Hospitalier Pitié-Salpêtriére, Paris, France
Search for more papers by this authorP. De Jonghe
University Hospital of Antwerp, Antwerp, Belgium
Institute Born-Bunge and University of Antwerp, Antwerp, Belgium
Search for more papers by this authorT. Lynch
Mater Misericordiae University, Beaumont & Mater Private Hospitals, Dublin, Ireland
Search for more papers by this authorC. Mariotti
IRCCS Foundation Neurological Institute Carlo Besta, Milan, Italy
Search for more papers by this authorA. Spinazzola
IRCCS Foundation Neurological Institute Carlo Besta, Milan, Italy
Search for more papers by this authorS. J. Tabrizi
Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
Search for more papers by this authorC. Tallaksen
Oslo University Hospital, and University of Oslo, Oslo, Norway
Search for more papers by this authorM. Zeviani
IRCCS Foundation Neurological Institute Carlo Besta, Milan, Italy
Search for more papers by this authorH. F. Harbo
Oslo University Hospital, and University of Oslo, Oslo, Norway
Search for more papers by this authorJ. Finsterer
Rudolfstiftung and Danube University, Krems, Vienna, Austria
Search for more papers by this authorJ. Baets
University Hospital of Antwerp, Antwerp, Belgium
Institute Born-Bunge and University of Antwerp, Antwerp, Belgium
Search for more papers by this authorC. Van Broeckhoven
Institute Born-Bunge and University of Antwerp, Antwerp, Belgium
Search for more papers by this authorS. Di Donato
IRCCS Foundation Neurological Institute Carlo Besta, Milan, Italy
Search for more papers by this authorB. Fontaine
Assistance Publique-Hôpitaux de Paris, Centre de référence des canalopathies musculaires, Groupe Hospitalier Pitié-Salpêtriére, Paris, France
Search for more papers by this authorP. De Jonghe
University Hospital of Antwerp, Antwerp, Belgium
Institute Born-Bunge and University of Antwerp, Antwerp, Belgium
Search for more papers by this authorT. Lynch
Mater Misericordiae University, Beaumont & Mater Private Hospitals, Dublin, Ireland
Search for more papers by this authorC. Mariotti
IRCCS Foundation Neurological Institute Carlo Besta, Milan, Italy
Search for more papers by this authorA. Spinazzola
IRCCS Foundation Neurological Institute Carlo Besta, Milan, Italy
Search for more papers by this authorS. J. Tabrizi
Institute of Neurology and National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
Search for more papers by this authorC. Tallaksen
Oslo University Hospital, and University of Oslo, Oslo, Norway
Search for more papers by this authorM. Zeviani
IRCCS Foundation Neurological Institute Carlo Besta, Milan, Italy
Search for more papers by this authorNils Erik Gilhus MD, PHD
Department of Clinical Medicine, University of Bergen, Norway
Department of Neurology, Haukeland University Hospital, Bergen, Norway
Search for more papers by this authorMichael P. Barnes MD, FRCP
University of Newcastle, Newcastle upon Tyne, UK
Hunters Moor Neurorehabilitation Ltd, Newcastle upon Tyne, UK
Search for more papers by this authorMichael Brainin MD
Department of Clinical Medicine and Prevention, Austria
Center for Clinical Neurosciences, Donau-Universität Krems, Austria
Department of Neurology, Landesklinikum Donauregion Tulln, Tulln, Austria
Search for more papers by this authorSummary
These EFNS guidelines on the molecular diagnosis of neurogenetic disorders are designed to provide practical help for the general neurologist to make appropriate use of molecular genetics in diagnosing neurogenetic disorders. Since the publication of the first two EFNS guideline papers on the molecular diagnosis of neurological diseases in 2001, rapid progress has been made in this field, necessitating an updated series of guidelines. This chapter provides updated guidelines for molecular diagnosis of Huntington's disease, Parkinson disease and dystonias, as well as a general introduction to the topic. Possibilities and limitations of molecular genetic diagnosis of these disorders are evaluated and recommendations are provided.
References
- Gasser, T, Dichgans, M, Finsterer, J, et al. EFNS Task Force on Molecular Diagnosis of Neurologic Disorders: guidelines for the molecular diagnosis of inherited neurologic diseases. Second of two parts. Eur J Neurol 2001; 8: 407–24.
- Gasser, T, Dichgans, M, Finsterer, J, et al. EFNS Task Force on Molecular Diagnosis of Neurologic Disorders: guidelines for the molecular diagnosis of inherited neurologic diseases. First of two parts. Eur J Neurol 2001; 8: 299–314.
- Brainin, M, Barnes, M, Baron, JC, et al. Guidance for the preparation of neurological management guidelines by EFNS scientific task forces–revised recommendation. 2004. Eur J Neurol 2004; 11: 577–81.
- The Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993; 72: 971–83.
- International Huntington Association (IHA) and the World Federation of Neurology (WFN) Research Group on Huntington's Chorea. Guidelines for the molecular genetics predictive test in Huntington's disease. Neurology 1994; 44: 1533–6.
- Wexler, NS, Lorimer, J, Porter, J, et al. Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset. Proc Natl Acad Sci U S A 2004; 101: 3498–503.
- Hayden, MR, Bombard, Y. Psychosocial effects of predictive testing for Huntington's disease. Adv Neurol 2005; 96: 226–39.
- Harper, PS, Gevers, S, de Wert, G, Creighton, S, Bombard, Y, Hayden, MR. Genetic testing and Huntington's disease: issues of employment. Lancet Neurol 2004; 3: 249–52.
- Scheidtmann, K, Schwarz, J, Holinski, E, Gasser, T, Trenkwalder, C. Paroxysmal choreoathetosis–a disorder related to Huntington's disease? J Neurol 1997; 244: 395–8.
- Wild, EJ, Tabrizi, SJ. Huntington's disease phenocopy syndromes. Curr Opin Neurol 2007; 20: 681–7.
- Kremer, B, Goldberg, P, Andrew, SE, et al. A worldwide study of the Huntington's disease mutation. The sensitivity and specificity of measuring CAG repeats. N Engl J Med 1994; 330: 1401–6.
- Holmes, SE, O'Hearn, E, Rosenblatt, A, et al. A repeat expansion in the gene encoding junctophilin-3 is associated with Huntington disease-lik. 2. Nat Genet 2001; 29: 377–8.
- Stevanin, G, Fujigasaki, H, Lebre, AS, et al. Huntington's disease-like phenotype due to trinucleotide repeat expansions in the TBP and JPH3 genes. Brain 2003; 126 (Pt 7): 1599–603.
- Koide, R, Ikeuchi, T, Onodera, O, et al. Unstable expansion of CAG repeat in hereditary dentatorubral-pallidoluysian atrophy (DRPLA). Nat Genet 1994; 6: 9–13.
- Moore, RC, Xiang, F, Monaghan, J, et al. Huntington disease phenocopy is a familial prion disease. Am J Hum Genet 2001; 69: 1385–8.
- Ueno, S, Maruki, Y, Nakamura, M, et al. The gene encoding a newly discovered protein, chorein, is mutated in chorea-acanthocytosis. Nat Genet 2001; 28: 121–2.
- Curtis, AR, Fey, C, Morris, CM, et al. Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. Nat Genet 2001; 28: 350–4.
- Wild, EJ, Mudanohwo, EE, Sweeney, MG, et al. Huntington's disease phenocopies are clinically and genetically heterogeneous. Mov Disord 2008; 23: 716–20.
- Gasser, T. Update on the genetics of Parkinson's disease. Mov Disord 2007; 22 (suppl 17): S343–50.
- Polymeropoulos, MH, Lavedan, C, Leroy, E, et al. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 1997; 276: 2045–7.
- Singleton, AB, Farrer, M, Johnson, J, et al. alpha-Synuclein locus triplication causes Parkinson's disease. Science 2003; 302. 841.
- Berg, D, Niwar, M, Maass, S, et al. Alpha-synuclein and Parkinson's disease: implications from the screening of more than 1,900 patients. Mov Disord 2005; 20: 1191–4.
- Ibanez, P, Lesage, S, Janin, S, et al. Alpha-synuclein gene rearrangements in dominantly inherited parkinsonism: frequency, phenotype, and mechanisms. Arch Neurol 2009; 66: 102–8.
- Zimprich, A, Biskup, S, Leitner, P, et al. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 2004; 44: 601–7.
- Berg, D, Schweitzer, K, Leitner, P, et al. Type and frequency of mutations in the LRRK2 gene in familial and sporadic Parkinson's disease*. Brain 2005; 128 (Pt 12): 3000–11.
- Gilks, WP, Abou-Sleiman, PM, Gandhi, S, et al. A common LRRK2 mutation in idiopathic Parkinson's disease. Lancet 2005; 365: 415–16.
- Ozelius, LJ, Senthil, G, Saunders-Pullman, R, et al. LRRK2 G2019S as a cause of Parkinson's disease in Ashkenazi Jews. N Engl J Med 2006; 354: 424–5.
- Orr -Urtreger, A, Shifrin, C, Rozovski, U, et al. The LRRK2 G2019S mutation in Ashkenazi Jews with Parkinson disease: is there a gender effect? Neurology 2007; 69: 1595–602.
- Lucking, CB, Durr, A, Bonifati, V, et al. Association between early-onset Parkinson's disease and mutations in the parkin gene. N Engl J Med 2000; 342: 1560–7.
- Aharon-Peretz, J, Rosenbaum, H, Gershoni-Baruch, R. Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews. N Engl J Med 2004; 351: 1972–7.
- Mata, IF, Samii, A, Schneer, SH, et al. Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders. Arch Neurol 2008; 65: 379–82.
- Ozelius, LJ, Hewett, JW, Page, CE, et al. The early-onset torsion dystonia gene (DYT1) encodes an ATP-binding protein. Nat Genet 1997; 17: 40–8.
- Bressman, SB, Sabatti, C, Raymond, D, et al. The DYT1 phenotype and guidelines for diagnostic testing. Neurology 2000; 54: 1746–52.
- Valente, EM, Warner, TT, Jarman, PR. et al. The role of DYT1 in primary torsion dystonia in Europe. Brain 1998; 121: 2335–9.
- Grundmann, K, Laubis-Herrmann, U, Bauer, I. et al. Frequency and phenotypic variability of the GAG deletion of the DYT1 gene in an unselected group of patients with dystonia. Arch Neurol 2003; 60: 1266–70.
- Ichinose, H, Ohye, T, Matsuda, Y, et al. Characterization of mouse and human GTP cyclohydrolase I genes. Mutations in patients with GTP cyclohydrolase I deficiency. J Biol Chem 1995; 270: 10062–71.
- Knappskog, PM, Flatmark, T, Mallet, J, Ludecke, B, Bartholome, K. Recessively inherited L -DOPA -responsive dystonia caused by a point mutation (Q381K) in the tyrosine hydroxylase gene. Hum Mol Genet 1995; 4: 1209–12.
- Hagenah, J, Saunders-Pullman, R, Hedrich, K, et al. High mutation rate in dopa-responsive dystonia: detection with comprehensive GCHI screening. Neurology 2005; 64: 908–11.
- Zimprich, A, Grabowski, M, Asmus, F, et al. Mutations in the gene encoding epsilon-sarcoglycan cause myoclonus-dystonia syndrome. Nat Genet 2001; 29: 66–9.
- Asmus, F, Zimprich, A, Tezenas Du, MS, et al. Myoclonus- dystonia syndrome: epsilon-sarcoglycan mutations and phenotype. Ann Neurol 2002; 52: 489–92.
- Grunewald, A, Djarmati, A, Lohmann-Hedrich, K, et al. Myoclonus-dystonia: significance of large SGCE deletions. Hum Mutat 2008; 29: 331–2.
- de Carvalho, AP, Sweadner, KJ, Penniston, JT, et al. Mutations in the Na+/K+-ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism. Neuron 2004; 43: 169–75.
- Suls, A, Dedeken, P, Goffin, K, et al. Paroxysmal exercise- induced dyskinesia and epilepsy is due to mutations in SLC2A1, encoding the glucose transporter GLUT1. Brain 2008; 131 (Pt 7): 1831–44.
- Tanzi, RE, Petrukhin, K, Chernov, I, et al. The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet 1993; 5: 344–50.
- Kitada, T, Asakawa, S, Hattori, N, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 1998; 392: 605–8.
- Valente, EM, bou-Sleiman, PM, Caputo, V, et al. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 2004; 304: 1158–60.
- Bonifati, V, Rizzu, P, van Baren, MJ, et al. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 2003; 299: 256–9.
- Ramirez, A, Heimbach, A, Grundemann, J, et al. Hereditary parkinsonism with dementia is caused by mutations in ATP13A2, encoding a lysosomal type 5 P-type ATPase. Nat Genet 2006; 38: 1184–91.
- Makino, S, Kaji, R, Ando, S, et al. Reduced neuron- specific expression of the TAF1 gene is associated with X-linked dystonia-parkinsonism. Am J Hum Genet 2007; 80: 393–406.
