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Spastic paraplegia due to recessive or dominant mutations in ERLIN2 can convert to ALS

Authors :
Jean-Philippe Camdessanché
Emilien Bernard
Jean-Christophe Antoine
Guillaume Banneau
Etienne Allart
Maria-Del-Mar Amador
François Muratet
Elisa Teyssou
Gabrielle Rudolf
Giovanni Stevanin
Christine Tranchant
Véronique Danel-Brunaud
Marie-Céline Fleury
Stéphanie Millecamps
Mathieu Anheim
Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM)
Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP]
Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
CHU Pitié-Salpêtrière [AP-HP]
Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Service de Neurologie et Pathologie du Mouvement, Hôpital Roger Salengro, Centre Hospitalier Universitaire (CHU) de Lille
CHU de Lille
Service de neurologie [CHU de Saint-Étienne]
Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne)
Service de Neurologie [CHU Strasbourg]
Hôpital de Hautepierre [Strasbourg]-Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg )
Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)
Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Service de Neurologie [Strasbourg]
CHU Strasbourg-Hopital Civil
Service de Neurologie [Hospices civils de Lyon - Hôpital Pierre Wertheimer]
Hospices Civils de Lyon (HCL)-Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL]
Hospices Civils de Lyon (HCL)
École pratique des hautes études (EPHE)
Université Paris sciences et lettres (PSL)
MILLECAMPS, Stéphanie
Institut du Cerveau = Paris Brain Institute (ICM)
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP]
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Source :
Neurology Genetics, Neurology Genetics, American Academy of Neurology, 2019, 5 (6), pp.e374. ⟨10.1212/NXG.0000000000000374⟩, Neurology Genetics, 2019, 5 (6), pp.e374. ⟨10.1212/NXG.0000000000000374⟩, Neurology: Genetics
Publication Year :
2019
Publisher :
HAL CCSD, 2019.

Abstract

ObjectiveThe aim of this study was to evaluate whether mutations in ERLIN2, known to cause SPG18, a recessive hereditary spastic paraplegia (SP) responsible for the degeneration of the upper motor neurons leading to weakness and spasticity restricted to the lower limbs, could contribute to amyotrophic lateral sclerosis (ALS), a distinct and more severe motor neuron disease (MND), in which the lower motor neurons also profusely degenerates, leading to tetraplegia, bulbar palsy, respiratory insufficiency, and ultimately the death of the patients.MethodsWhole-exome sequencing was performed in a large cohort of 200 familial ALS and 60 sporadic ALS after a systematic screening for C9orf72 hexanucleotide repeat expansion. ERLIN2 variants identified by exome analysis were validated using Sanger analysis. Segregation of the identified variant with the disease was checked for all family members with available DNA.ResultsHere, we report the identification of ERLIN2 mutations in patients with a primarily SP evolving to rapid progressive ALS, leading to the death of the patients. These mutations segregated with the disease in a dominant (V168M) or recessive (D300V) manner in these families or were found in apparently sporadic cases (N125S).ConclusionsInheritance of ERLIN2 mutations appears to be, within the MND spectrum, more complex that previously reported. These results expand the clinical phenotype of ERLIN2 mutations to a severe outcome of MND and should be considered before delivering a genetic counseling to ERLIN2-linked families.

Details

Language :
English
ISSN :
23767839
Database :
OpenAIRE
Journal :
Neurology Genetics, Neurology Genetics, American Academy of Neurology, 2019, 5 (6), pp.e374. ⟨10.1212/NXG.0000000000000374⟩, Neurology Genetics, 2019, 5 (6), pp.e374. ⟨10.1212/NXG.0000000000000374⟩, Neurology: Genetics
Accession number :
edsair.doi.dedup.....a2a3379500d7161cc4bc824b5bbdbe27
Full Text :
https://doi.org/10.1212/NXG.0000000000000374⟩