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Rudenskaya G.E.

Research Centre for Medical Genetics

Kadnikova V.A.

Research Centre for Medical Genetics

Sidorova O.P.

Vladimirsky Moscow Regional Clinical Institute

Beetz C.

Department of Clinical Chemistry and Laboratory Diagnostics of the Jena University Hospital

Illarioshkin S.N.

Research Center of Neurology

Dadaly E.L.

Research Centre for Medical Genetics

Proskokova T.N.

Far East State Medical University

Ryzhkova O.P.

Research Centre for Medical Genetics

Hereditary spastic paraplegia type 4 (SPG4) in Russian patients

Authors:

Rudenskaya G.E., Kadnikova V.A., Sidorova O.P., Beetz C., Illarioshkin S.N., Dadaly E.L., Proskokova T.N., Ryzhkova O.P.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2019;119(11): 11‑20

DOI: 10.17116/jnevro201911911111

Read: 10957 times

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Table of contents

HEREDITARY SPASTIC PARAPLEGIA TYPE 4 (SPG4) IN RUSSIAN PATIENTS
HEREDITARY SPASTIC PARAPLEGIA TYPE 4 (SPG4) IN RUSSIAN PATIENTS

To cite this article:

Rudenskaya GE, Kadnikova VA, Sidorova OP, et al. Hereditary spastic paraplegia type 4 (SPG4) in Russian patients. S.S. Korsakov Journal of Neurology and Psychiatry. 2019;119(11):11‑20. (In Russ.)
https://doi.org/10.17116/jnevro201911911111

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)
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Abstract:

OBJECTIVE

To investigate molecular, clinical and genealogical characteristics of SPG4 in a first representative Russian group, to estimate SPG4 proportion among all DNA-diagnosed spastic paraplegias.

MATERIAL AND METHODS

Fifty unrelated Russian families with SPG4 detected in the course of clinical and molecular studies of spastic paraplegias were studied. Clinical, genealogical and several molecular methods were used, i.e. Sanger sequencing of SPAST, massive parallel sequencing MPS (panel «hereditary paraplegias») and multiplex ligation-dependent amplification MLPA.

RESULTS

SPG4 proportion was 56% among all DNA verified SPG cases (90 families/14 forms) and 68% in subgroup of dominant SPG. In 50 families, 43 different SPAST mutations were detected, of which 21 were novel; percentage of large rearrangements was 30% (13 mutations in 15 families). Four mutations were detected in two families each, nonsense mutation c.1291C>T (p.Arg431*) in 4 unrelated families. Proportion of familial cases was 68%, pedigrees with “missing” disease in elderly carriers pointed to incomplete penetrance. Age of onset varied from one year to 58 years, middle-age onset was common but the proportion of early-onset cases, particularly in male index cases, was also high. Onset age showed marked intrafamilial differences (more than 10 years in 14 pedigrees, up to 50 year in one) and between families with identical mutations. Insidious onset, slow development with most patients ambulant and «uncomplicated» phenotype were typical. Cases with additional signs were: a family with ataxia in both patients, two families with epilepsy in one of SPG4 patients; three families with mild mental deficiency in one of SPG4 patients. A case described separately is a 29-year-old male patient with indeterminate myalgia and no SPG signs in whom SPAST previously reported mutation p.Ala430Thr de novo was an unexpected MPS finding.

CONCLUSION

SPG4 substantially predomimates in SPG structure in Russian families as practically everywhere else. Half of 43 detected SPAST mutations are novel, the proportion of large rearrangements is 30% higher than in most of studies. Clinical inter- and intrafamilial variability concerns mostly age of onset. SPG4 is not exclusively adult-onset as was thought earlier.

Keywords:

SPG4
SPAST mutations
Sanger sequencing
massive exome sequencing MPS
clinical variability
additional symptoms

Authors:

Rudenskaya G.E.

Research Centre for Medical Genetics

Kadnikova V.A.

Research Centre for Medical Genetics

Sidorova O.P.

Vladimirsky Moscow Regional Clinical Institute

Beetz C.

Department of Clinical Chemistry and Laboratory Diagnostics of the Jena University Hospital

Illarioshkin S.N.

Research Center of Neurology

Dadaly E.L.

Research Centre for Medical Genetics

Proskokova T.N.

Far East State Medical University

Ryzhkova O.P.

Research Centre for Medical Genetics

Received:

23.05.2019

Accepted:

28.06.2019

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References:

  1. OMIM (On-line Mendelian Inheritance in Man) https://www.ncbi.nlm.nih.gov/omim
  2. Rudenskaya GE, Kadnikova VA, Ryzhkova OP. Common forms of hereditary spastic paraplegias. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova. 2019;119(2):77-87. (In Russ). https://doi.org/10.17116/jnevro201911902194
  3. Chrestian N, Dupré N, Gan-Or Z, Szuto A, Chen S, Venkitachalam A, Brisson JD, Warman-Chardon J, Ahmed S, Ashtiani S, MacDonald H, Mohsin N, Mourabit-Amari K, Provencher P, Boycott KM, Stavropoulos DJ, Dion PA, Ray PN, Suchowersky O, Rouleau GA, Yoon G. Clinical and genetic study of hereditary spastic paraplegia in Canada. Neurol Genet. 2016;3(1):e122. eCollection.
  4. Schüle R, Wiethoff S, Martus P, Karle KN, Otto S, Klebe S, Klimpe S, Gallenmüller C, Kurzwelly D, Henkel D, Rimmele F, Stolze H, Kohl Z, Kassubek J, Klockgether T, Vielhaber S, Kamm C, Klopstock T, Bauer P, Züchner S, Liepelt-Scarfone I, Schöls L. Hereditary spastic paraplegia: Clinicogenetic lessons from 608 patients. Ann Neurol. 2016;79(4):646-658.  https://doi.org/10.1002/ana.24611
  5. Koh K, Ishiura H, Tsuji S, Takiyama Y. JASPAC: Japan Spastic Paraplegia Research Consortium. Brain Sci. 2018;8(8). pii: E153. https://doi.org/10.3390/brainsci8080153
  6. Rudenskaia GE, Sermyagina IG, Illarioshkin SN, Sidorova OP, Fedotov VP, Polyakov AV. Hereditary spastic paraplegia, type 4 (SPG4): clinical and molecular genetic characteristics. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova. 2010;110(6):12-19. (In Russ).
  7. Rudenskaya GE, Kadnikova VA, Konovalov FA, Zakharova EYu, Polyakov AV. Hereditary spastic paraplegias and genocopies: up-to-date diagnostic possibilities. Parkinson disease and movement disorders. Handbook on materials of VI National Congress. M. 2017. (In Russ).
  8. Shchagina OA, Tverskaya SM, Kadnikova VA, Polyakov AV. DNA diagnostics of periodic disease. Meditsinskaya Genetika. 2006;10:29-32. (In Russ).
  9. Illarioshkin SN, Rudenskaya GE, Ivanova-Smolenskaya IA, Markova ED, Klyushnikov SA. Nasledstvennie ataxii i papaplegii. M. 2006. (In Russ).
  10. Loureiro JL, Brandão E, Ruano L, Brandão AF, Lopes AM, Thieleke-Matos C, Miller-Fleming L, Cruz VT, Barbosa M, Silveira I, Stevanin G, Pinto-Basto J, Sequeiros J, Alonso I, Coutinho P. Autosomal dominant spastic paraplegias: a review of 89 families resulting from a Portuguese survey. JAMA Neurol. 2013;70(4):481-487.  https://doi.org/10.1001/jamaneurol.2013.1956
  11. Dong EL, Wang C, Wu S, Lu YQ, Lin XH, Su HZ, Zhao M, He J, Ma LX, Wang N, Chen WJ, Lin X. Clinical spectrum and genetic landscape for hereditary spastic paraplegias in China. Mol Neurodegener. 2018;13(1):36.  https://doi.org/10.1186/s13024-018-0269-1
  12. Erichsen AK, Koht J, Stray-Pedersen A, Abdelnoor M, Tallaksen CM. Prevalence of hereditary ataxia and spastic paraplegia in southeast Norway: a population-based study. Brain. 2009;132:1577-1588. https://doi.org/10.1093/brain/awp056
  13. Alvarez V, Sánchez-Ferrero E, Beetz C, Díaz M, Alonso B, Corao AI, Gámez J, Esteban J, Gonzalo JF, Pascual-Pascual SI, López de Munain A, Moris G, Ribacoba R, Márquez C, Rosell J, Marín R, García-Barcina MJ, Del Castillo E, Benito C, Coto E; Group for the Study of the Genetics of Spastic Paraplegia. Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia. BMC Neurol. 2010;10:89.  https://doi.org/10.1186/1471-2377-10-89
  14. Elert-Dobkowska E, Stepniak I, Krysa W, Rajkiewicz M, Rakowicz M, Sobanska A, Rudzinska M, Wasielewska A, Pilch J, Kubalska J, Lipczynska-Lojkowska W, Kulczycki J, Kurdziel K, Sikorska A, Beetz C, Zaremba J, Sulek A. Molecular spectrum of the SPAST, ATL1 and REEP1 gene mutations associated with the most common hereditary spastic paraplegias in a group of Polish patients. J Neurol Sci. 2015;359(1-2):35-39.  https://doi.org/10.1016/j.jns.2015.10.030
  15. Human Gene Mutation Database (HGMD) Professional 2017.1  https://portal.biobase-international.com
  16. Shoukier M, Neesen J, Sauter SM, Argyriou L, Doerwald N, Pantakani DV, Mannan AU. Expansion of mutation spectrum, determination of mutation cluster regions and predictive structural classification of SPAST mutations in hereditary spastic paraplegia. Eur J Hum Genet. 2009;17(2):187-194.  https://doi.org/10.1038/ejhg.2008.147
  17. de Bot ST, van den Elzen RT, Mensenkamp AR, Schelhaas HJ, Willemsen MA, Knoers NV, Kremer HP, van de Warrenburg BP, Scheffer H. Hereditary spastic paraplegia due to SPAST mutations in 151 Dutch patients: new clinical aspects and 27 novel mutations. J Neurol Neurosurg Psychiatry. 2010;81(10):1073-1078. https://doi.org/10.1136/jnnp.2009.201103
  18. Magariello A, Muglia M, Patitucci A, Ungaro C, Mazzei R, Gabriele AL, Sprovieri T, Citrigno L, Conforti FL, Liguori M, Gambardella A, Bono F, Piccoli T, Patti F, Zappia M, Mancuso M, Iemolo F, Quattrone A. Mutation analysis of the SPG4 gene in Italian patients with pure and complicated forms of spastic paraplegia. J Neurol Sci. 2010;288(1-2):96-100.  https://doi.org/10.1016/j.jns.2009.09.025
  19. Sulek A, Elert E, Rajkiewicz M, Zdzienicka E, Stepniak I, Krysa W, Zaremba J. Screening for the hereditary spastic paraplaegias SPG4 and SPG3A with the multiplex ligation-dependent probe amplification technique in a large population of affected individuals. Neurol Sci. 2013;34(2):239-242.  https://doi.org/10.1007/s10072-011-0899-3
  20. Racis L, Tessa A, Di Fabio R, Storti E, Agnetti V, Casali C, Santorelli FM, Pugliatti M. The high prevalence of hereditary spastic paraplegia in Sardinia, insular Italy. J Neurol. 2014;261(1):52-59.  https://doi.org/10.1007/s00415-013-7151-4
  21. Meijer IA, Dupré N, Brais B, Cossette P, St-Onge J, Rioux MF, Benard M, Rouleau GA. SPG4 founder effect in French Canadians with hereditary spastic paraplegia. Can J Neurol Sci. 2007;34(2):211-214.  https://doi.org/10.1017/50317167100006065
  22. Akhmetgaleyeva AF, Khidiyatova IM, Saifullina EV, Magzhanov RF, Idrisova RV, Khusnutdinova EK. Two novel mutations in gene SPG4 in patients with autosomal dominant spastic paraplegia. Genetika. 2016;52(6):603-607 (In Russ.). https://doi.org/10.7868/S0016675816060023
  23. Lan MY, Chang YY, Yeh TH, Lai SC, Liou CW, Kuo HC, Wu YR, Lyu RK, Hung JW, Chang YC, Lu CS. High frequency of SPG4 in Taiwanese families with autosomal dominant hereditary spastic paraplegia. BMC Neurol. 2014;14:216.  https://doi.org/10.1186/s12883-014-0216-x
  24. Parodi L, Fenu S, Barbier M, Banneau G, Duyckaerts C, Tezenas du Montcel S, Monin ML, Ait Said S, Guegan J, Tallaksen CME, Sablonniere B, Brice A, Stevanin G, Depienne C, Durr A; SPATAX network. Spastic paraplegia due to SPAST mutations is modified by the underlying mutation and sex. Brain. 2018;141(12):3331-3342. https://doi.org/10.1093/brain/awy285
  25. Solowska JM, Baas PW. Hereditary spastic paraplegia SPG4: what is known and not known about the disease. Brain. 2015;138:2471-2484. https://doi.org/10.1093/brain/awv178
  26. Hensiek A, Kirker S, Reid E. Diagnosis, investigation and management of hereditary spastic paraplegias in the era of next generation sequencing. J Neurol. 2015;262(7):1601-1612. https://doi.org/10.1007/s00415-014-7598-y
  27. Tallaksen C, Guichart-Gomez E, Verpillat P. Hahn-Barma V, Ruberg M, Fontaine B, Brice A, Dubois B, Durr A. Subtle cognitive impairment but no dementia in patients with spastin mutations. Arch Neurol. 2003;60:1113-1118.
  28. Erichsen AK, Server AI, Landri L, Sandvik CME. Tallaksen, Proton magnetic resonance spectroscopy and cognition in patients with spastin mutations. J Neurol Sci. 2009;277(1-2):124-129.  https://doi.org/10.1016/j.jns.2008.10.030
  29. Lo Giudice T, Lombardi F, Santorelli FM, Kawarai T, Orlacchio A. Hereditary spastic paraplegia: clinical-genetic characteristics and evolving molecular mechanisms. Exp Neurol. 2014;261:518-539.  https://doi.org/10.1016/j.expneurol.2014.06.011
  30. Chamard L, Ferreira S, Pijoff A, Silvestre M, Berger E, Magnin E. Cognitive impairment involving social cognition in SPG4 hereditary spastic paraplegia. Behav Neurol. 2016;6423461. https://doi.org/10.1155/2016/6423461
  31. Miura S, Shibata H, Kida H, Noda K, Toyama T, Iwasaki N, Iwaki A, Ayabe M, Aizawa H, Taniwaki T, Fukumaki Y. Partial SPAST and DPY30 deletions in a Japanese spastic paraplegia type 4 family. Neurogenetics. 2011;12(1):25-31.  https://doi.org/10.1007/s10048-010-0260-7
  32. Tisher A, Salardini A. A case report of a woman with young onset cognitive impairment associated with hereditary spastic paraplegia due to a mutation in the SPAST gene. J Neurol Sci. 2016;367:131-132.  https://doi.org/10.1016/j.jns.2016.05.057
  33. Ribai P, Depienne C, Fedirko E, Jothy A, Viveweger C, Hahn-Barma V, Brice A, Durr A. Mental deficiency in three families with SPG4 spastic paraplegia. Europ J Hum Genet. 2008;16:97-104.  https://doi.org/10.1038/sj.ejhg.5201922
  34. Mead S, Proukakis C, Wood N, Crosby AH, Plant GT, Warner TT. A large family with hereditary spastic paraparesis due to a frame shift mutation of the spastin (SPG4) gene: association with multiple sclerosis in two affected siblings and epilepsy in other affected family members. J Neurol Neurosurg Psychiat. 2001;71:788-791.  https://doi.org/10.1136/jnnp.71.6.788
  35. Bertelli M, Cecchin S, Lorusso L Sidoti V, Fabbri A, Lapucci C, Buda A, Pandolfo M. Identification of a novel mutation in the spastin gene (SPG4) in an Italian family with hereditary spastic paresis. Panminerva Med. 2006;48:193-197. 
  36. Nielsen JE, Johnsen B, Koefoed P, Scheuer KH, Grønbech-Jensen M, Law I, Krabbe K, Nørremølle A, Eiberg H, Søndergård H, Dam M, Rehfeld JF, Krarup C, Paulson OB, Hasholt L, Sørensen SA. Hereditary spastic paraplegia with cerebellar ataxia: a complex phenotype associated with a new SPG4 gene mutation. Eur J Neurol. 2004;11:817-824.  https://doi.org/10.1111/j.1468-1331.2004.00888.x
  37. Tsuchiya M, Koh K, Ishida A, Ichinose Y, Shindo K, Takiyama Y. A Japanese family with a novel nonsense mutation in the spastin gene associated with both cerebellar ataxia and cognitive impairment. J Neurol Sci. 2018;397:114-116.  https://doi.org/10.1016/j.jns.2018.12.025
  38. Newton T, Allison R, Edgar JR, Lumb JH, Rodger CE, Manna PT, Rizo T, Kohl Z, Nygren AOH, Arning L, Schüle R, Depienne C, Goldberg L, Frahm C, Stevanin G, Durr A, Schöls L, Winner B, Beetz C, Reid E. Mechanistic basis of an epistatic interaction reducing age at onset in hereditary spastic paraplegia. Brain. 2018;141(5):1286-1299. https://doi.org/10.1093/brain/awy034
  39. Chelban V, Tucci A, Lynch DS, Polke JM, Santos L, Jonvik H, Groppa S, Wood NW, Houlden H. Truncating mutations in SPAST patients are associated with a high rate of psychiatric comorbidities in hereditary spastic paraplegia. J Neurol Neurosurg Psychiatry. 2017;88(8):681-687.  https://doi.org/10.1136/jnnp-2017-315796
  40. Svenstrup K, Bross P, Koefoed P, Hjermind LE, Eiberg H, Born AP, Vissing J, Gyllenborg J, Nørremølle A, Hasholt L, Nielsen JE. Sequence variants in SPAST, SPG3A and HSPD1 in hereditary spastic paraplegia. J Neurol Sci. 2009;284(1-2):90-95.  https://doi.org/10.1016/j.jns.2009.04.024
  41. de Souza PVS, Bortholin T, Naylor FG, de Rezende Pinto WB, Oliveira AS. Infantile-onset ascending spastic paraplegia phenotype associated with SPAST mutation. J Neurol Sci. 2016;371:34-35.  https://doi.org/10.1016/j.jns.2016.10.017
  42. Scarlato M, Nuara A, Gerevini S, Benedetti S, Rossi P, Ferrari M, Previtali SC. A new double-trouble phenotype: fascioscapulohumeral muscular dystrophy ameliorates hereditary spastic paraparesis due to spastin mutation. J Neurol. 2015;262(2):476-478.  https://doi.org/10.1007/s00415-014-7606-2
  43. Chelban V, Lynch D, Houlden H, Wood N. Triple trouble: a striking new phenotype or competing genes in a family with hereditary spastic paraplegia. J Neurology. 2016;236(6):1232-1233. https://doi.org/10.1007/s00415-016-8103-6
  44. Rudenskaya GE, Kadnikova VA, Ryzkova OP. Hereditary spastic paraplegias in the era of next generation sequencing: genetic diversity, epidemiology, classification. Meditsinskaya Genetika. 2018;8:3-12. (In Russ.).
  45. Elert-Dobkowska E, Stepniak I, Krysa W, Ziora-Jakutowicz K, Rakowicz M, Sobanska A, Pilch J, Antczak-Marach D, Zaremba J, Sulek A. Next-generation sequencing study reveals the broader variant spectrum of hereditary spastic paraplegia and related phenotypes. Neurogenetics. 2019;20(1):27-38.  https://doi.org/10.1007/s10048-019-00565-6
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