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A panel study on patients with dominant cerebellar ataxia highlights the frequency of channelopathies.

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Coutelier, Marie [UCL] Coarelli, Giulia Monin, Marie-Lorraine Konop, Juliette Davoine, Claire-Sophie Sznajer, Yves [UCL] SPATAX network

Autosomal dominant cerebellar ataxias have a marked heterogeneous genetic background, with mutations in 34 genes identified so far. This large amount of implicated genes accounts for heterogeneous clinical presentations, making genotype-phenotype correlations a major challenge in the field. While polyglutamine ataxias, linked to CAG repeat expansions in genes such as ATXN1, ATXN2, ATXN3, ATXN7, CACNA1A and TBP, have been extensively characterized in large cohorts, there is a need for comprehensive assessment of frequency and phenotype of more 'conventional' ataxias. After exclusion of CAG/polyglutamine expansions in spinocerebellar ataxia genes in 412 index cases with dominantly inherited cerebellar ataxias, we aimed to establish the relative frequencies of mutations in other genes, with an approach combining panel sequencing and TaqMan® polymerase chain reaction assay. We found relevant genetic variants in 59 patients (14.3%). The most frequently mutated were channel genes [CACNA1A (n = 16), KCND3 (n = 4), KCNC3 (n = 2) and KCNA1 (n = 2)]. Deletions in ITPR1 (n = 11) were followed by biallelic variants in SPG7 (n = 9). Variants in AFG3L2 (n = 7) came next in frequency, and variants were rarely found in STBN2 (n = 2), ELOVL5, FGF14, STUB1 and TTBK2 (n = 1 each). Interestingly, possible risk factor variants were detected in SPG7 and POLG. Clinical comparisons showed that ataxias due to channelopathies had a significantly earlier age at onset with an average of 24.6 years, versus 40.9 years for polyglutamine expansion spinocerebellar ataxias and 37.8 years for SPG7-related forms (P = 0.001). In contrast, disease duration was significantly longer in the former (20.5 years versus 9.3 and 13.7, P=0.001), though for similar functional stages, indicating slower progression of the disease. Of interest, intellectual deficiency was more frequent in channel spinocerebellar ataxias, while cognitive impairment in adulthood was similar among the three groups. Similar differences were found among a single gene group, comparing 23 patients with CACNA1A expansions (spinocerebellar ataxia 6) to 22 patients with CACNA1A point mutations, which had lower average age at onset (25.2 versus 47.3 years) with longer disease duration (18.7 versus 10.9), but lower severity indexes (0.39 versus 0.44), indicating slower progression of the disease. In conclusion, we identified relevant genetic variations in up to 15% of cases after exclusion of polyglutamine expansion spinocerebellar ataxias, and confirmed CACNA1A and SPG7 as major ataxia genes. We could delineate firm genotype-phenotype correlations that are important for genetic counselling and of possible prognostic value.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2017
Language Anglais
Journal information "Brain : a journal of neurology" - Vol. 140, no.6, p. 1579-1594 (2017)
Peer reviewed yes
Publisher Oxford University Press ((United Kingdom) Oxford)
issn 0006-8950
e-issn 1460-2156
Publication status Publié
Affiliations UCL - SSS/DDUV - Institut de Duve
UCL - SSS/IREC/SLUC - Pôle St.-Luc
UCL - (SLuc) Centre de génétique médicale UCL
MESH Subject ATPases Associated with Diverse Cellular Activities ; Adolescent ; Adult ; Age of Onset ; Aged ; Aged, 80 and over ; Calcium Channels ; Cerebellar Ataxia ; Channelopathies ; Child ; Child, Preschool ; Cohort Studies ; Female ; Genes, Dominant ; Genotype ; Humans ; Male ; Metalloendopeptidases ; Middle Aged ; Phenotype ; Young Adult
Keywords CACNA1A ; SPG7 ; cerebellar ataxia ; channelopathies
Links
  1. Brain, 131, 338 (2008)
  2. Bakalkin Georgy, Watanabe Hiroyuki, Jezierska Justyna, Depoorter Cloë, Verschuuren-Bemelmans Corien, Bazov Igor, Artemenko Konstantin A., Yakovleva Tatjana, Dooijes Dennis, Van de Warrenburg Bart P.C., Zubarev Roman A., Kremer Berry, Knapp Pamela E., Hauser Kurt F., Wijmenga Cisca, Nyberg Fred, Sinke Richard J., Verbeek Dineke S., Prodynorphin Mutations Cause the Neurodegenerative Disorder Spinocerebellar Ataxia Type 23, 10.1016/j.ajhg.2010.10.001
  3. Baruffini Enrico, Lodi Tiziana, Dallabona Cristina, Puglisi Andrea, Zeviani Massimo, Ferrero Iliana, Genetic and chemical rescue of the Saccharomyces cerevisiae phenotype induced by mitochondrial DNA polymerase mutations associated with progressive external ophthalmoplegia in humans, 10.1093/hmg/ddl219
  4. Bourassa Cynthia V., Meijer Inge A., Merner Nancy D., Grewal Kanwal K., Stefanelli Mark G., Hodgkinson Kathleen, Ives Elizabeth J., Pryse-Phillips William, Jog Mandar, Boycott Kym, Grimes David A., Goobie Sharan, Leckey Richard, Dion Patrick A., Rouleau Guy A., VAMP1 Mutation Causes Dominant Hereditary Spastic Ataxia in Newfoundland Families, 10.1016/j.ajhg.2012.07.018
  5. Brkanac Zoran, Spencer David, Shendure Jay, Robertson Peggy D., Matsushita Mark, Vu Tiffany, Bird Thomas D., Olson Maynard V., Raskind Wendy H., IFRD1 Is a Candidate Gene for SMNA on Chromosome 7q22-q23, 10.1016/j.ajhg.2009.04.008
  6. Browne David L., Gancher Stephen T., Nutt John G., Brunt Ewout R. P., Smith Eric A., Kramer Patricia, Litt Michael, Episodic ataxia/myokymia syndrome is associated with point mutations in the human potassium channel gene, KCNA1, 10.1038/ng1094-136
  7. Burusnukul Prinyarat, de los Reyes Emily C., Phenotypic Variations in 3 Children With POLG1 Mutations, 10.1177/0883073808324539
  8. Cadieux-Dion Maxime, Turcotte-Gauthier Maude, Noreau Anne, Martin Caroline, Meloche Caroline, Gravel Micheline, Drouin Christian Allen, Rouleau Guy A., Nguyen Dang Khoa, Cossette Patrick, Expanding the Clinical Phenotype Associated WithELOVL4Mutation : Study of a Large French-Canadian Family With Autosomal Dominant Spinocerebellar Ataxia and Erythrokeratodermia, 10.1001/jamaneurol.2013.6337
  9. Casari Giorgio, De Fusco Maurizio, Ciarmatori Sonia, Zeviani Massimo, Mora Marina, Fernandez Patricio, De Michele Giuseppe, Filla Alessandro, Cocozza Sergio, Marconi Roberto, Dürr Alexandre, Fontaine Bertrand, Ballabio Andrea, Spastic Paraplegia and OXPHOS Impairment Caused by Mutations in Paraplegin, a Nuclear-Encoded Mitochondrial Metalloprotease, 10.1016/s0092-8674(00)81203-9
  10. Chen Dong-Hui, Brkanac Zoran, Christophe Verlinde L.M.J., Tan Xiao-Jian, Bylenok Laura, Nochlin David, Matsushita Mark, Lipe Hillary, Wolff John, Fernandez Magali, Cimino P.J., Thomas Bird D., Raskind Wendy H., Missense Mutations in the Regulatory Domain of PKCγ: A New Mechanism for Dominant Nonepisodic Cerebellar Ataxia, 10.1086/373883
  11. Chinnery P. F., Keers S. M., Holden M. J., Ramesh V., Dalton A., Infantile hereditary spastic paraparesis due to codominant mutations in the spastin gene, 10.1212/01.wnl.0000135346.63675.3e
  12. Coutelier Marie, Blesneac Iulia, Monteil Arnaud, Monin Marie-Lorraine, Ando Kunie, Mundwiller Emeline, Brusco Alfredo, Le Ber Isabelle, Anheim Mathieu, Castrioto Anna, Duyckaerts Charles, Brice Alexis, Durr Alexandra, Lory Philippe, Stevanin Giovanni, A Recurrent Mutation in CACNA1G Alters Cav3.1 T-Type Calcium-Channel Conduction and Causes Autosomal-Dominant Cerebellar Ataxia, 10.1016/j.ajhg.2015.09.007
  13. Coutelier M., Burglen L., Mundwiller E., Abada-Bendib M., Rodriguez D., Chantot-Bastaraud S., Rougeot C., Cournelle M.-A., Milh M., Toutain A., Bacq D., Meyer V., Afenjar A., Deleuze J.-F., Brice A., Heron D., Stevanin G., Durr A., GRID2 mutations span from congenital to mild adult-onset cerebellar ataxia, 10.1212/wnl.0000000000001524
  14. Coutelier Marie, Stevanin Giovanni, Brice Alexis, Genetic landscape remodelling in spinocerebellar ataxias: the influence of next-generation sequencing, 10.1007/s00415-015-7725-4
  15. David Gilles, Abbas Nacer, Stevanin Giovanni, Dürr Alexandra, Yvert Gaël, Cancel Géraldine, Weber Chantal, Imbert Georges, Saudou Frédéric, Antoniou Eric, Drabkin Harry, Gemmill Robert, Giunti Paola, Benomar Ali, Wood Nick, Ruberg Merle, Agid Yves, Mandel Jean-Louis, Brice Alexis, Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion, 10.1038/ng0997-65
  16. Brain, 137, 2657 (2014)
  17. Di Bella Daniela, Lazzaro Federico, Brusco Alfredo, Plumari Massimo, Battaglia Giorgio, Pastore Annalisa, Finardi Adele, Cagnoli Claudia, Tempia Filippo, Frontali Marina, Veneziano Liana, Sacco Tiziana, Boda Enrica, Brussino Alessandro, Bonn Florian, Castellotti Barbara, Baratta Silvia, Mariotti Caterina, Gellera Cinzia, Fracasso Valentina, Magri Stefania, Langer Thomas, Plevani Paolo, Di Donato Stefano, Muzi-Falconi Marco, Taroni Franco, Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28, 10.1038/ng.544
  18. Di Gregorio Eleonora, Borroni Barbara, Giorgio Elisa, Lacerenza Daniela, Ferrero Marta, Lo Buono Nicola, Ragusa Neftj, Mancini Cecilia, Gaussen Marion, Calcia Alessandro, Mitro Nico, Hoxha Eriola, Mura Isabella, Coviello Domenico A., Moon Young-Ah, Tesson Christelle, Vaula Giovanna, Couarch Philippe, Orsi Laura, Duregon Eleonora, Papotti Mauro Giulio, Deleuze Jean-François, Imbert Jean, Costanzi Chiara, Padovani Alessandro, Giunti Paola, Maillet-Vioud Marcel, Durr Alexandra, Brice Alexis, Tempia Filippo, Funaro Ada, Boccone Loredana, Caruso Donatella, Stevanin Giovanni, Brusco Alfredo, ELOVL5 Mutations Cause Spinocerebellar Ataxia 38, 10.1016/j.ajhg.2014.07.001
  19. Duarri Anna, Jezierska Justyna, Fokkens Michiel, Meijer Michel, Schelhaas Helenius J., den Dunnen Wilfred F. A., van Dijk Freerk, Verschuuren-Bemelmans Corien, Hageman Gerard, van de Vlies Pieter, Küsters Benno, van de Warrenburg Bart P., Kremer Berry, Wijmenga Cisca, Sinke Richard J., Swertz Morris A., Kampinga Harm H., Boddeke Erik, Verbeek Dineke S., Mutations in potassium channelkcnd3cause spinocerebellar ataxia type 19, 10.1002/ana.23700
  20. Durr Alexandra, Autosomal dominant cerebellar ataxias: polyglutamine expansions and beyond, 10.1016/s1474-4422(10)70183-6
  21. Elleuch N., Depienne C., Benomar A., Hernandez A. M. O., Ferrer X., Fontaine B., Grid D., Tallaksen C.M.E., Zemmouri R., Stevanin G., Durr A., Brice A., Mutation analysis of the paraplegin gene (SPG7) in patients with hereditary spastic paraplegia, 10.1212/01.wnl.0000201185.91110.15
  22. Escayg Andrew, De Waard Michel, Lee David D., Bichet Delphine, Wolf Peter, Mayer Thomas, Johnston Janine, Baloh Robert, Sander Thomas, Meisler Miriam H., Coding and Noncoding Variation of the Human Calcium-Channel β4-Subunit Gene CACNB4 in Patients with Idiopathic Generalized Epilepsy and Episodic Ataxia, 10.1086/302909
  23. Fogel Brent L., Hanson Sonya M., Becker Esther B. E., Do mutations in the murine ataxia geneTRPC3cause cerebellar ataxia in humans? : Letters: New Observations, 10.1002/mds.26096
  24. Fogel Brent L., Lee Hane, Deignan Joshua L., Strom Samuel P., Kantarci Sibel, Wang Xizhe, Quintero-Rivera Fabiola, Vilain Eric, Grody Wayne W., Perlman Susan, Geschwind Daniel H., Nelson Stanley F., Exome Sequencing in the Clinical Diagnosis of Sporadic or Familial Cerebellar Ataxia, 10.1001/jamaneurol.2014.1944
  25. Gomez Christopher M., Das Soma, Clinical Exome Sequencing : The New Standard in Genetic Diagnosis, 10.1001/jamaneurol.2014.2015
  26. Graziewicz Maria A., Longley Matthew J., Copeland William C., DNA Polymerase γ in Mitochondrial DNA Replication and Repair, 10.1021/cr040463d
  27. Hekman K. E., Yu G.-Y., Brown C. D., Zhu H., Du X., Gervin K., Undlien D. E., Peterson A., Stevanin G., Clark H. B., Pulst S. M., Bird T. D., White K. P., Gomez C. M., A conserved eEF2 coding variant in SCA26 leads to loss of translational fidelity and increased susceptibility to proteostatic insult, 10.1093/hmg/dds392
  28. Holmes Susan E, O'Hearn Elizabeth E, McInnis Melvin G, Gorelick-Feldman Daniel A, Kleiderlein John J, Callahan Colleen, Kwak Noeun G, Ingersoll-Ashworth Roxann G, Sherr Meeia, Sumner August J, Sharp Alan H, Ananth Uma, Seltzer William K, Boss Michael A, Vieria-Saecker Ana-Maria, Epplen Jörg T, Riess Olaf, Ross Christopher A, Margolis Russell L, Expansion of a novel CAG trinucleotide repeat in the 5′ region of PPP2R2B is associated with SCA12, 10.1038/70493
  29. Hopkins Sarah E., Somoza Arthur, Gilbert Donald L., Rare Autosomal Dominant POLG1 Mutation in a Family With Metabolic Strokes, Posterior Column Spinal Degeneration, and Multi-Endocrine Disease, 10.1177/0883073809343313
  30. Brain, 129, 1674 (2006)
  31. Houlden Henry, Johnson Janel, Gardner-Thorpe Christopher, Lashley Tammaryn, Hernandez Dena, Worth Paul, Singleton Andrew B, Hilton David A, Holton Janice, Revesz Tamas, Davis Mary B, Giunti Paolo, Wood Nicholas W, Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11, 10.1038/ng.2007.43
  32. Brain, 131, 329 (2008)
  33. Ikeda Yoshio, Dick Katherine A, Weatherspoon Marcy R, Gincel Dan, Armbrust Karen R, Dalton Joline C, Stevanin Giovanni, Dürr Alexandra, Zühlke Christine, Bürk Katrin, Clark H Brent, Brice Alexis, Rothstein Jeffrey D, Schut Lawrence J, Day John W, Ranum Laura P W, Spectrin mutations cause spinocerebellar ataxia type 5, 10.1038/ng1728
  34. Jen J. C., Wan J., Palos T. P., Howard B. D., Baloh R. W., Mutation in the glutamate transporter EAAT1 causes episodic ataxia, hemiplegia, and seizures, 10.1212/01.wnl.0000172638.58172.5a
  35. Jodice C., Mantuano E., Veneziano L., Trettel F., Sabbadini G., Calandriello L., Francia A., Spadaro M., Pierelli F., Salvi F., Ophoff R. A., Frants R. R., Frontali M., Episodic Ataxia Type 2 (EA2) and Spinocerebellar Ataxia Type 6 (SCA6) Due to CAG Repeat Expansion in the CACNA1A Gene on Chromosome 19p, 10.1093/hmg/6.11.1973
  36. Kasiviswanathan Rajesh, Copeland William C., Biochemical analysis of the G517V POLG variant reveals wild-type like activity, 10.1016/j.mito.2011.08.003
  37. Kawaguchi Yoshiya, Okamoto Toshihiro, Taniwaki Masafumi, Aizawa Megumi, Inoue Miho, Katayama Sadao, Kawakami Hideshi, Nakamura Shigenobu, Nishimura Masaki, Akiguchi Ichiro, Kimura Jun, Narumiya Shuh, Kakizuka Akira, CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1, 10.1038/ng1194-221
  38. Keogh M. J., Steele H., Douroudis K., Pyle A., Duff J., Hussain R., Smertenko T., Griffin H., Santibanez-Koref M., Horvath R., Chinnery P. F., Frequency of rare recessive mutations in unexplained late onset cerebellar ataxia, 10.1007/s00415-015-7772-x
  39. Brain, 135, 2980 (2012)
  40. Kobayashi Hatasu, Abe Koji, Matsuura Tohru, Ikeda Yoshio, Hitomi Toshiaki, Akechi Yuji, Habu Toshiyuki, Liu Wanyang, Okuda Hiroko, Koizumi Akio, Expansion of Intronic GGCCTG Hexanucleotide Repeat in NOP56 Causes SCA36, a Type of Spinocerebellar Ataxia Accompanied by Motor Neuron Involvement, 10.1016/j.ajhg.2011.05.015
  41. Koide R., Ikeuchi T., Onodera O., Tanaka H., Igarashi S., Endo K., Takahashi H., Kondo R., Ishikawa A., Hayashi T., Saito M., Tomoda A., Miike T., Naito H., Ikuta F., Tsuji S., Unstable expansion of CAG repeat in hereditary dentatorubral–pallidoluysian atrophy (DRPLA), 10.1038/ng0194-9
  42. Koide R, A neurological disease caused by an expanded CAG trinucleotide repeat in the TATA-binding protein gene: a new polyglutamine disease? [In Process Citation], 10.1093/hmg/8.11.2047
  43. Koob Michael D., Moseley Melinda L., Schut Lawrence J., Benzow Kellie A., Bird Thomas D., Day John W., Ranum Laura P.W., An untranslated CTG expansion causes a novel form of spinocerebellar ataxia (SCA8), 10.1038/7710
  44. Lamantea Eleonora, Tiranti Valeria, Bordoni Andreina, Toscano Antonio, Bono Francesco, Servidei Serena, Papadimitriou Alex, Spelbrink Hans, Silvestri Laura, Casari Giorgio, Comi Giacomo P., Zeviani Massimo, Mutations of mitochondrial DNA polymerase ?A are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia, 10.1002/ana.10278
  45. Lee Yi-Chung, Durr Alexandra, Majczenko Karen, Huang Yen-Hua, Liu Yu-Chao, Lien Cheng-Chang, Tsai Pei-Chien, Ichikawa Yaeko, Goto Jun, Monin Marie-Lorraine, Li Jun Z., Chung Ming-Yi, Mundwiller Emeline, Shakkottai Vikram, Liu Tze-Tze, Tesson Christelle, Lu Yi-Chun, Brice Alexis, Tsuji Shoji, Burmeister Margit, Stevanin Giovanni, Soong Bing-Wen, Mutations inKCND3cause spinocerebellar ataxia type 22, 10.1002/ana.23701
  46. Li H., Durbin R., Fast and accurate short read alignment with Burrows-Wheeler transform, 10.1093/bioinformatics/btp324
  47. Luoma Petri T., Luo Ningguang, Löscher Wolfgang N., Farr Carol L., Horvath Rita, Wanschitz Julia, Kiechl Stefan, Kaguni Laurie S., Suomalainen Anu, Functional defects due to spacer-region mutations of human mitochondrial DNA polymerase in a family with an ataxia-myopathy syndrome, 10.1093/hmg/ddi196
  48. Marelli C., Cazeneuve C., Brice A., Stevanin G., Dürr A., Autosomal dominant cerebellar ataxias, 10.1016/j.neurol.2011.01.015
  49. Arch Neurol, 68, 637 (2011)
  50. Matsuura Tohru, Fang Ping, Lin Xi, Khajavi Mehrdad, Tsuji Kuniko, Rasmussen Astrid, Grewal Raji P., Achari Madhureeta, Alonso Maria E., Pulst Stefan M., Zoghbi Huda Y., Nelson David L., Roa Benjamin B., Ashizawa Tetsuo, Somatic and Germline Instability of the ATTCT Repeat in Spinocerebellar Ataxia Type 10, 10.1086/421526
  51. McKenna A., Hanna M., Banks E., Sivachenko A., Cibulskis K., Kernytsky A., Garimella K., Altshuler D., Gabriel S., Daly M., DePristo M. A., The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data, 10.1101/gr.107524.110
  52. Monin Marie-Lorraine, Tezenas du Montcel Sophie, Marelli Cecilia, Cazeneuve Cecile, Charles Perrine, Tallaksen Chantal, Forlani Sylvie, Stevanin Giovanni, Brice Alexis, Durr Alexandra, Survival and severity in dominant cerebellar ataxias, 10.1002/acn3.156
  53. Moseley Melinda L, Zu Tao, Ikeda Yoshio, Gao Wangcai, Mosemiller Anne K, Daughters Randy S, Chen Gang, Weatherspoon Marcy R, Clark H Brent, Ebner Timothy J, Day John W, Ranum Laura P W, Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8, 10.1038/ng1827
  54. Brain, 136, 3106 (2013)
  55. Novarino G., Fenstermaker A. G., Zaki M. S., Hofree M., Silhavy J. L., Heiberg A. D., Abdellateef M., Rosti B., Scott E., Mansour L., Masri A., Kayserili H., Al-Aama J. Y., Abdel-Salam G. M. H., Karminejad A., Kara M., Kara B., Bozorgmehri B., Ben-Omran T., Mojahedi F., Mahmoud I. G. E. D., Bouslam N., Bouhouche A., Benomar A., Hanein S., Raymond L., Forlani S., Mascaro M., Selim L., Shehata N., Al-Allawi N., Bindu P. S., Azam M., Gunel M., Caglayan A., Bilguvar K., Tolun A., Issa M. Y., Schroth J., Spencer E. G., Rosti R. O., Akizu N., Vaux K. K., Johansen A., Koh A. A., Megahed H., Durr A., Brice A., Stevanin G., Gabriel S. B., Ideker T., Gleeson J. G., Exome Sequencing Links Corticospinal Motor Neuron Disease to Common Neurodegenerative Disorders, 10.1126/science.1247363
  56. Obayashi Masato, Ishikawa Kinya, Izumi Yuishin, Takahashi Makoto, Niimi Yusuke, Sato Nozomu, Onodera Osamu, Kaji Ryuji, Nishizawa Masatoyo, Mizusawa Hidehiro, Prevalence of inositol 1, 4, 5-triphosphate receptor type 1 gene deletion, the mutation for spinocerebellar ataxia type 15, in Japan screened by gene dosage, 10.1038/jhg.2012.5
  57. Ophoff Roel A, Terwindt Gisela M, Vergouwe Monique N, van Eijk Ronald, Oefner Peter J, Hoffman Susan M.G, Lamerdin Jane E, Mohrenweiser Harvey W, Bulman Dennis E, Ferrari Maurizio, Haan Joost, Lindhout Dick, van Ommen Gert-Jan B, Hofker Marten H, Ferrari Michel D, Frants Rune R, Familial Hemiplegic Migraine and Episodic Ataxia Type-2 Are Caused by Mutations in the Ca2+ Channel Gene CACNL1A4, 10.1016/s0092-8674(00)81373-2
  58. Orr Harry T., Chung Ming-yi, Banfi Sandro, Kwiatkowski Thomas J., Servadio Antonio, Beaudet Arthur L., McCall Alanna E., Duvick Lisa A., Ranum Laura P. W., Zoghbi Huda Y., Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1, 10.1038/ng0793-221
  59. Pfeffer G., Pyle A., Griffin H., Miller J., Wilson V., Turnbull L., Fawcett K., Sims D., Eglon G., Hadjivassiliou M., Horvath R., Nemeth A., Chinnery P. F., SPG7 mutations are a common cause of undiagnosed ataxia, 10.1212/wnl.0000000000001369
  60. Pulst Stefan-M., Nechiporuk Alex, Nechiporuk Tamilla, Gispert Suzana, Chen Xiao-Ning, Lopes-Cendes Iscia, Pearlman Susan, Starkman Sidney, Orozco-Diaz Guillermo, Lunkes Astrid, DeJong Pieter, Rouleau Guy A., Auburger Georg, Korenberg Julie R., Figueroa Carla, Sahba Soodabeh, Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2, 10.1038/ng1196-269
  61. Brain, 138, 276 (2015)
  62. Richards Sue, , Aziz Nazneen, Bale Sherri, Bick David, Das Soma, Gastier-Foster Julie, Grody Wayne W., Hegde Madhuri, Lyon Elaine, Spector Elaine, Voelkerding Karl, Rehm Heidi L., Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, 10.1038/gim.2015.30
  63. Roxburgh Richard H., Marquis-Nicholson Renate, Ashton Fern, George Alice M., Lea Rod A., Eccles David, Mossman Stuart, Bird Thomas, van Gassen Koen L., Kamsteeg Erik-Jan, Love Donald R., The p.Ala510Val mutation in the SPG7 (paraplegin) gene is the most common mutation causing adult onset neurogenetic disease in patients of British ancestry, 10.1007/s00415-012-6792-z
  64. Ruano Luis, Melo Claudia, Silva M. Carolina, Coutinho Paula, The Global Epidemiology of Hereditary Ataxia and Spastic Paraplegia: A Systematic Review of Prevalence Studies, 10.1159/000358801
  65. Russell Jonathan F., Steckley Jamie L., Coppola Giovanni, G. Hahn Angelika F., Howard MacKenzie A., Kornberg Zachary, Huang Alden, Mirsattari Seyed M., Merriman Barry, Klein Eric, Choi Murim, Lee Hsien-Yang, Kirk Andrew, Nelson-Williams Carol, Gibson Gillian, Baraban Scott C., Lifton Richard P., Geschwind Daniel H., Fu Ying-Hui, Ptáček Louis J., Familial cortical myoclonus with a mutation in NOL3, 10.1002/ana.23666
  66. Sánchez-Ferrero E, Coto E, Beetz C, Gámez J, Corao AI, Díaz M, Esteban J, del Castillo E, Moris G, Infante J, Menéndez M, Pascual-Pascual SI, López de Munaín A, Garcia-Barcina MJ, Alvarez V, SPG7mutational screening in spastic paraplegia patients supports a dominant effect for some mutations and a pathogenic role for p.A510V, 10.1111/j.1399-0004.2012.01896.x
  67. Sato Nozomu, Amino Takeshi, Kobayashi Kazuhiro, Asakawa Shuichi, Ishiguro Taro, Tsunemi Taiji, Takahashi Makoto, Matsuura Tohru, Flanigan Kevin M., Iwasaki Sawa, Ishino Fumitoshi, Saito Yuko, Murayama Shigeo, Yoshida Mari, Hashizume Yoshio, Takahashi Yuji, Tsuji Shoji, Shimizu Nobuyoshi, Toda Tatsushi, Ishikawa Kinya, Mizusawa Hidehiro, Spinocerebellar Ataxia Type 31 Is Associated with “Inserted” Penta-Nucleotide Repeats Containing (TGGAA)n, 10.1016/j.ajhg.2009.09.019
  68. Sawyer Sarah L., Schwartzentruber Jeremy, Beaulieu Chandree L., Dyment David, Smith Amanda, Chardon Jodi Warman, Yoon Grace, Rouleau Guy A., Suchowersky Oksana, Siu Victoria, Murphy Lisa, Hegele Robert A., Marshall Christian R., Bulman Dennis E., Majewski Jacek, Tarnopolsky Mark, Boycott Kym M., , Exome Sequencing as a Diagnostic Tool for Pediatric-Onset Ataxia, 10.1002/humu.22451
  69. Schöls Ludger, Bauer Peter, Schmidt Thorsten, Schulte Thorsten, Riess Olaf, Autosomal dominant cerebellar ataxias: clinical features, genetics, and pathogenesis, 10.1016/s1474-4422(04)00737-9
  70. Schulte C., Synofzik M., Gasser T., Schols L., ATAXIA WITH OPHTHALMOPLEGIA OR SENSORY NEUROPATHY IS FREQUENTLY CAUSED BY POLG MUTATIONS, 10.1212/wnl.0b013e3181b78488
  71. Shi Yuting, Wang Junling, Li Jia-Da, Ren Haigang, Guan Wenjuan, He Miao, Yan Weiqian, Zhou Ying, Hu Zhengmao, Zhang Jianguo, Xiao Jingjing, Su Zheng, Dai Meizhi, Wang Jun, Jiang Hong, Guo Jifeng, Zhou Yafang, Zhang Fufeng, Li Nan, Du Juan, Xu Qian, Hu Yacen, Pan Qian, Shen Lu, Wang Guanghui, Xia Kun, Zhang Zhuohua, Tang Beisha, Identification of CHIP as a Novel Causative Gene for Autosomal Recessive Cerebellar Ataxia, 10.1371/journal.pone.0081884
  72. Stevanin Giovanni, Herman Alexandra, Dürr Alexandra, Jodice Carla, Frontali Marina, Agid Yves, Brice Alexis, Are (CTG)n expansions at the SCA8 locus rare polymorphisms?, 10.1038/73408
  73. Tsoi Ho, Yu Allen C S, Chen Zhefan S, Ng Nelson K N, Chan Anne Y Y, Yuen Liz Y P, Abrigo Jill M, Tsang Suk Ying, Tsui Stephen K W, Tong Tony M F, Lo Ivan F M, Lam Stephen T S, Mok Vincent C T, Wong Lawrence K S, Ngo Jacky C K, Lau Kwok-Fai, Chan Ting-Fung, Chan H Y Edwin, A novel missense mutation inCCDC88Cactivates the JNK pathway and causes a dominant form of spinocerebellar ataxia, 10.1136/jmedgenet-2014-102333
  74. van de Leemput Joyce, Chandran Jayanth, Knight Melanie A., Holtzclaw Lynne A., Scholz Sonja, Cookson Mark R., Houlden Henry, Gwinn-Hardy Katrina, Fung Hon-Chung, Lin Xian, Hernandez Dena, Simon-Sanchez Javier, Wood Nick W., Giunti Paola, Rafferty Ian, Hardy John, Storey Elsdon, Gardner R. J. McKinlay, Forrest Susan M., Fisher Elizabeth M. C., Russell James T., Cai Huaibin, Singleton Andrew B., Deletion at ITPR1 Underlies Ataxia in Mice and Spinocerebellar Ataxia 15 in Humans, 10.1371/journal.pgen.0030108
  75. Van Goethem Gert, Dermaut Bart, Löfgren Ann, Martin Jean-Jacques, Van Broeckhoven Christine, Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions, 10.1038/90034
  76. van Swieten John C., Brusse Esther, de Graaf Bianca M., Krieger Elmar, van de Graaf Raoul, de Koning Inge, Maat-Kievit Anneke, Leegwater Peter, Dooijes Dennis, Oostra Ben A., Heutink Peter, A Mutation in the Fibroblast Growth Factor 14 Gene Is Associated with Autosomal Dominant Cerebral Ataxia, 10.1086/345488
  77. Vidal Ruben, Frangione Blas, Rostagno Agueda, Mead Simon, Révész Tamas, Plant Gordon, Ghiso Jorge, A stop-codon mutation in the BRI gene associated with familial British dementia, 10.1038/21637
  78. Brain, 133, 3510 (2010)
  79. Wang K., Li M., Hakonarson H., ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data, 10.1093/nar/gkq603
  80. Waters Michael F, Minassian Natali A, Stevanin Giovanni, Figueroa Karla P, Bannister John P A, Nolte Dagmar, Mock Allan F, Evidente Virgilio Gerald H, Fee Dominic B, Müller Ulrich, Dürr Alexandra, Brice Alexis, Papazian Diane M, Pulst Stefan M, Mutations in voltage-gated potassium channel KCNC3 cause degenerative and developmental central nervous system phenotypes, 10.1038/ng1758
  81. Winkelmann Juliane, Lin Ling, Schormair Barbara, Kornum Birgitte R., Faraco Juliette, Plazzi Giuseppe, Melberg Atle, Cornelio Ferdinando, Urban Alexander E., Pizza Fabio, Poli Francesca, Grubert Fabian, Wieland Thomas, Graf Elisabeth, Hallmayer Joachim, Strom Tim M., Mignot Emmanuel, Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness and narcolepsy, 10.1093/hmg/dds035
  82. Worth Paul F., Houlden Henry, Giunti Paola, Davis Mary B., Wood Nicholas W., Large, expanded repeats in SCA8 are not confined to patients with cerebellar ataxia, 10.1038/73411
  83. Yue Qing, Jen Joanna C., Nelson Stanley F., Baloh Robert W., Progressive Ataxia Due to a Missense Mutation in a Calcium-Channel Gene, 10.1086/301613
  84. Zhuchenko Olga, Bailey Jennifer, Bonnen Penelope, Ashizawa Tetsuo, Stockton David W., Amos Chris, Dobyns William B., Subramony S.H., Zoghbi Huda Y., Lee Cheng Chi, Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansions in the α1A-voltage-dependent calcium channel, 10.1038/ng0197-62
  85. Züchner Stephan, Wang Gaofeng, Tran-Viet Khanh-Nhat, Nance Martha A., Gaskell Perry C., Vance Jeffery M., Ashley-Koch Allison E., Pericak-Vance Margaret A., Mutations in the Novel Mitochondrial Protein REEP1 Cause Hereditary Spastic Paraplegia Type 31, 10.1086/505361
Bibliographic reference Coutelier, Marie ; Coarelli, Giulia ; Monin, Marie-Lorraine ; Konop, Juliette ; Davoine, Claire-Sophie ; et. al. A panel study on patients with dominant cerebellar ataxia highlights the frequency of channelopathies.. In: Brain : a journal of neurology, Vol. 140, no.6, p. 1579-1594 (2017)
Permanent URL http://hdl.handle.net/2078.1/204630