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Spastic paraplegia due to recessive or dominant mutations in ERLIN2 can convert to ALS
- 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.
- Subjects :
- Hereditary spastic paraplegia
[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics
Article
03 medical and health sciences
0302 clinical medicine
C9orf72
medicine
Spasticity
Amyotrophic lateral sclerosis
Exome
Tetraplegia
Genetics (clinical)
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
Bulbar palsy
Genetics
0303 health sciences
business.industry
[SCCO.NEUR]Cognitive science/Neuroscience
[SCCO.NEUR] Cognitive science/Neuroscience
medicine.disease
[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics
Neurology (clinical)
medicine.symptom
business
Trinucleotide repeat expansion
030217 neurology & neurosurgery
Subjects
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⟩