Putative founder effect in the Polish, Iranian and United States populations for the L144S SOD1 mutation associated with slowly uniform phenotype of amyotrophic lateral sclerosis

Abstract

Mutations in SOD1 cause approximately 12–25% of familial ALS and ≈2% of apparently sporadic ALS cases. Clinical phenotypes linked to SOD1 mutations are heterogeneous and intra-familial variability of the clinical phenotype is frequently observed. SOD1 L144S mutation, identified also in Brazil, Iran and United States, is the second most frequent mutation among ALS patients in Poland. So far, 10 FALS pedigrees with SOD1 L144S mutation have been reported worldwide. The aim of the study was to establish the origin of SOD1 L144S mutation in geographically distinct populations. The clinical presentation of the Polish patients was compared with those from the previously reported populations (26 ever-reported patients). Clinically, L144S mutation is associated with both sporadic and familial ALS of relatively slow uniform course, a prevalent onset in the lower limbs, either classic or PMA presentation and a long survival time. Like in the case of other previously described SOD1 mutations, there was an intra-familial heterogeneity and reduced penetrance for ALS was observed. We propose that the L144S SOD1 mutation in the three studied populations has a common founder most likely of Polish origin.

Keywords:

• Amyotrophic lateral sclerosis
• SOD1
• mutation
• L144S
• STR markers

Acknowledgements

The authors thank the patients and their families for their cooperation. Dr. Peter Sapp sadly passed away at the time of manuscript preparation. The authors wish to thank Prof. Robert H. Brown Jr. for the possibility to use the US samples for the current study and a critical reading of the manuscript.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

The study was partially supported by the National Science Center Poland (NCN) project SONATA9 [UMO-2015/17/D/NZ2/03712], and EU Joint Program – Neurodegenerative Disease Research (JPND) projects SOPHIA (5/SOPHIA/JPND/2012) and OnWEBDUALS (DZP/2/JPND-III/2015). The project is supported through the following funding organizationsunder the egis of JPND – www.jpnd.eu: Germany, Bundesministerium für Bildung und Forschung (BMBF); Poland, Narodowe Centrum Badań i Rozwoju (NCBiR); Portugal, Fundação a Ciência e a Tecnologia (FCT); Sweden, Vetenskapsrådet (VR), France, Agence Nationale de la Recherche; Ireland, Health Research Board; Italy, Ministero della Salute; The Netherlands, The Netherlands Organization for Health Research and Development; Spain, Ministerio de Ciencia e Innovación; Switzerland, Schweizerischer Nationalfonds zur Förderung der wissenschaftlichen Forschung; Turkey, Tübitak; United Kingdom, Medical Research Council.