Genetic background of the hereditary spastic paraplegia phenotypes in Hungary - An analysis of 58 probands

Peter Balicza, Zoltan Grosz, Michael A. Gonzalez, Renata Bencsik, Klara Pentelenyi, Aniko Gal, Edina Varga, Peter Klivenyi, Julia Koller, Stephan L Zuchner, Judit Maria Molnar

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Background Hereditary spastic paraplegias (HSPs) are a clinically and genetically heterogeneous group of neurodegenerative diseases with progressive lower limb spasticity and weakness. The aim of this study is to determine the frequency of different SPG mutations in Hungarian patients, and to provide further genotype-phenotype correlations for the known HSP causing genes. Methods We carried out genetic testing for 58 probands with clinical characteristics of HSP. For historical reasons, three different approaches were followed in different patients: 1) Sanger sequencing of ATL1 and SPAST genes, 2) whole exome, and 3) targeted panel sequencing by next generation sequencing. Results Genetic diagnosis was established for 20 probands (34.5%). We detected nine previously unreported mutations with high confidence for pathogenicity. The most frequently affected gene was SPAST with pathogenic or likely pathogenic mutations in 10 probands. The most frequently detected variant in our cohort was the SPG7 p.Leu78∗, observed in four probands. Altogether five probands were diagnosed with SPG7. Additional mutations were detected in SPG11, ATL1, NIPA1, and ABCD1. Conclusion This is the first comprehensive genetic epidemiological study of patients with HSP in Hungary. Next generation sequencing improved the yield of genetic diagnostics in this disease group even when the phenotype was atypical. However, considering the frequency of the HSP-causing gene defects, SPG4, the most common form of the disease, should be tested first to be cost effective in this economic region.

Original languageEnglish (US)
Pages (from-to)116-121
Number of pages6
JournalJournal of the Neurological Sciences
Volume364
DOIs
StatePublished - May 15 2016

Keywords

  • Ethnic distribution
  • Hereditary spastic paraplegia
  • SPAST
  • Spastic paraplegia
  • Spastin
  • SPG4
  • SPG7

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

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    Balicza, P., Grosz, Z., Gonzalez, M. A., Bencsik, R., Pentelenyi, K., Gal, A., Varga, E., Klivenyi, P., Koller, J., Zuchner, S. L., & Molnar, J. M. (2016). Genetic background of the hereditary spastic paraplegia phenotypes in Hungary - An analysis of 58 probands. Journal of the Neurological Sciences, 364, 116-121. https://doi.org/10.1016/j.jns.2016.03.018