Intermediate C9orf72 repeat numbers are not ALS risk factors

Kevin Mouzat (1, 2) , Jovana Kantar (1, 2) , Anne Polge (1, 2) , Hélène Blasco (3) , Philippe Corcia (4) , Philippe Couratier (5, 6) , Pierre Clavelou (7) , Raoul Juntas-Morales (8) , Nicolas Pageot (8) , Serge Lumbroso (1) , William Camu (8)

1 Laboratoire de Biochimie [CHRU Nîmes]
2 UM - Université de Montpellier
3 Service de Médecine Nucléaire, CHRU de Tours, boulevard Tonnellé, 37000 Tours, France ; INSERM U930, Université François Rabelais, boulevard Tonnellé, 37000 Tours, France ; INSERM CIC 1415, boulevard Tonnellé, 37000 Tours, France.
4 Laboratoire de Biochimie [CHRU Tours]
5 Service de Neurologie [CHU Limoges]
6 NET - Neuroépidémiologie Tropicale
7 Service de Neurologie [CHU Clermont-Ferrand]
8 SLA CHRU Montpellier - Centre référent Sclérose Latérale Amyotrophique [CHRU Montpellier]

Introduction: Amyotrophic lateral sclerosis (ALS) is one of the most severe motor neuron (MN) disorders in adults. The C9orf72 repeat expansion is the most common genetic cause of the disease. Initial findings have set the pathogenic cut-off to 30 repeat. However, intermediate repeat numbers between 16 and 30 have also been proposed to be associated with ALS risk. As most studies rely on ALS patients, we performed a case-control study in a French cohort to understand the involvement of intermediate repeats on the ALS risk. Methods: In a cohort of 412 C9orf72-negative sporadic ALS patients and 327 healthy controls, the C9orf72 repeat number was assessed by Repeat-Primed PCR. Results: The most frequent alleles were two, five and eight repeats both in ALS and control groups. The highest repeat number was 22 in controls and 26 in patients. The allelic distribution was not significantly different between both groups. Conclusions: These findings show a lack of association between C9orf72 intermediate repeat numbers and the risk of developing ALS. These data suggest that repeat numbers below 30 are not an ALS risk factor in the French population and confirms the definition of the C9orf72 pathogenic cut-off.

Mots clés: genetics; C9orf72; hexanucleotide repeats

Domaines: Sciences du Vivant [q-bio]; Santé publique et épidémiologie

Kevin Mouzat, Jovana Kantar, Anne Polge, Hélène Blasco, Philippe Corcia, et al.. Intermediate C9orf72 repeat numbers are not ALS risk factors. 28th International Symposium on ALS/MND, Dec 2017, Boston, United States. 18 (Supplément S2), pp.92-93, 2017, Amyotrophic Lateral Sclerosis and Frontotemporal. ⟨hal-01658048⟩