Acta Neuropathologica

, Volume 137, Issue 5, pp 855–858 | Cite as

An ALS case with 38 (G4C2)-repeats in the C9orf72 gene shows TDP-43 and sparse dipeptide repeat protein pathology

  • Lieselot Dedeene
  • Evelien Van Schoor
  • Valérie Race
  • Matthieu Moisse
  • Rik Vandenberghe
  • Koen Poesen
  • Philip Van Damme
  • Dietmar Rudolf ThalEmail author

The (G4C2)-hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72) is the most common mutation linked to amyotrophic lateral sclerosis (ALS), as it accounts for 51.6% of the familial ALS cases and 9.6% of the sporadic ALS cases [1, 2]. This repeat expansion also underlies approximately 25% of the familial frontotemporal lobar degeneration (FTLD) cases [12]. The pathogenic (G4C2)-repeat length is estimated to range from hundreds to thousands of repeat units, whereas neurologically healthy controls usually show a repeat length of only 2–30 (G4C2)-repeats [3]. However, the threshold for the repeat length to drive or aggravate ALS pathology is still under debate. Some ALS or FTLD cases show an intermediate (G4C2)-repeat length of 30–90 (G4C2)-repeats in peripheral blood DNA [4, 5, 7, 11], while, in contrast, some 30–70 repeat carriers did not develop symptomatic disease [6, 8]. Several cases with this so-called intermediate repeat length in peripheral blood DNA...


Amyotrophic lateral sclerosis C9orf72 repeat expansion Dipeptide repeat proteins Transactive response DNA-binding protein 43 kDa 



LD is funded by a PhD Fellowship of the Research Foundation–Flanders (FWO-Vlaanderen) (1165119N). EVS is funded by an SB PhD Fellowship of FWO-Vlaanderen (1S46219N). PVD holds a senior clinical investigatorship of FWO-Vlaanderen and is supported by the ALS Liga Belgium and the KU Leuven ALS funds ‘Een hart voor ALS’ and ‘Laeversfonds voor ALS onderzoek’. PVD and DRT received C1-internal funds from KU Leuven (C14-17–107). DRT and RV received funding from FWO-Odysseus Grant no. G0F8516N and Vlaamse Impulsfinanciering voor Netwerken voor Dementie Onderzoek (VIND, IWT 135043). We thank Bruno Van Keirsbilck, Alicja Ronisz, Simona Ospitalieri, Petra Weckx and Marta Koper for technical support.

Supplementary material

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Supplementary material 1 (DOCX 3055 KB)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurosciences, Laboratory for Molecular Neurobiomarker ResearchKU Leuven, Leuven Brain Institute (LBI)LeuvenBelgium
  2. 2.Department of Neurosciences, Laboratory for NeuropathologyKU Leuven, Leuven Brain Institute (LBI)LeuvenBelgium
  3. 3.Laboratory MedicineUniversity Hospitals LeuvenLeuvenBelgium
  4. 4.Department of Neurosciences, Laboratory for Neurobiology, KU Leuven and Center for Brain & Disease ResearchVIB, Leuven Brain Institute (LBI)LeuvenBelgium
  5. 5.Laboratory for Molecular Diagnostics, Center for Human GeneticsKU LeuvenLeuvenBelgium
  6. 6.Department of Neurosciences, Laboratory for Cognitive NeurologyKU Leuven, Leuven Brain Institute (LBI)LeuvenBelgium
  7. 7.Department of NeurologyUniversity Hospitals LeuvenLeuvenBelgium
  8. 8.Department of PathologyUniversity Hospitals LeuvenLeuvenBelgium

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