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Mutations in UBQLN2 are rare in French amyotrophic lateral sclerosis |
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| Authors: | Millecamps Stéphanie Corcia Philippe Cazeneuve Cécile Boillée Séverine Seilhean Danielle Danel-Brunaud Véronique Vandenberghe Nadia Pradat Pierre-François Le Forestier Nadine Lacomblez Lucette Bruneteau Gaëlle Camu William Brice Alexis Meininger Vincent LeGuern Eric Salachas François |
| Affiliation: | 1. Centre de Recherche de l''Institut du Cerveau et de la Moelle Epinière, INSERM UMR_S975, CNRS UMR7225, Université Pierre et Marie Curie-Paris, Hôpital Pitié-Salpêtrière, Paris, France;2. Centre SLA, CHU de Tours, Université François Rabelais, Tours, France;3. Assistance Publique Hôpitaux de Paris (AP-HP), Département de Génétique et Cytogénétique, Unité Fonctionnelle de neurogénétique moléculaire et cellulaire, Hôpital Pitié-Salpêtrière, Paris, France;4. Département de Neuropathologie, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France;5. Service de Neurologie et Pathologie du Mouvement, Hôpital Roger Salengro, CHRU Lille, France;6. Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Bron, France;g Fédération des Maladies du Système Nerveux, APHP, Centre de référence maladies rares SLA, Hôpital Pitié-Salpêtrière, Paris, France;h Service de Neurologie, Hôpital Guy de Chauliac, Université de Montpellier I, Montpellier France |
| Abstract: | Mutations in UBQLN2 encoding ubiquilin-2 have recently been identified in families with dominant X-linked juvenile and adult-onset amyotrophic lateral sclerosis (ALS) and ALS/dementia. Ubiquilin-2 is a component of the ubiquitin inclusions detected in degenerating neurons in ALS patients. All the previously reported UBQLN2 mutations were localized in 1 of the 12 PXX domains of ubiquilin-2 protein. We sequenced UBQLN2 in 130 French patients with familial ALS (FALS) and absence of male-to-male transmission and the PXX domain in 240 more patients with sporadic ALS (SALS). We identified, at the heterozygote state, the c.1500_1508delCATAGGCCC, p.Gly502_Ile504del, in 1 affected woman. This deletion presumably leads to the in-frame deletion of 1 PXX repeat in the protein. This variant did not segregate with the disease in the corresponding family and was also detected in 1/380 control subject. Our results suggest that UBQLN2 gene mutations are rare in French ALS. |
| Keywords: | Motor neuron disease Amyotrophic lateral sclerosis Familial ALS Genetic analysis PXX repeat domain UBQLN2 deletion |
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