High-throughput sequencing revealed a novel SETX mutation in a Hungarian patient with amyotrophic lateral sclerosis

Kornélia Tripolszki , Dóra Török , David Goudenège (1) , Katalin Farkas , Adrienn Sulák , Nóra Török , József Engelhardt , Péter Klivényi , Vincent Procaccio (1) , Nikoletta Nagy , Márta Széll

1 MITOVASC - MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of the motor neurons. To date, 126 genes have been implicated in ALS. Therefore, the heterogenous genetic background of ALS requires comprehensive genetic investigative approaches.

METHODS: In this study, DNA from 28 Hungarian ALS patients was subjected to targeted high-throughput sequencing of the coding regions of three Mendelian ALS genes: , and .

RESULTS: A novel heterozygous missense mutation (c.791A>G, p.N264S) of the gene was identified in a female patient presenting an atypical ALS phenotype, including adult onset and lower motor neuron impairment. No further mutations were detected in the other Mendelian ALS genes investigated.

CONCLUSION: Our study contributes to the understanding of the genetic and phenotypic diversity of motor neuron diseases (MNDs). Our results also suggest that the elucidation of the genetic background of MNDs requires a complex approach, including the screening of both Mendelian and non-Mendelian genes.

Mots clés: RNA-Binding Protein FUS; Humans; Mutation; Missense; Phenotype; proteins; RNA Helicases; High-Throughput Nucleotide Sequencing; Heterozygote; Female; C9orf72 Protein; amyotrophic lateral sclerosis; Aged

Domaines: Médecine humaine et pathologie

Kornélia Tripolszki, Dóra Török, David Goudenège, Katalin Farkas, Adrienn Sulák, et al.. High-throughput sequencing revealed a novel SETX mutation in a Hungarian patient with amyotrophic lateral sclerosis. Brain and Behavior, 2017, 7 (4), pp.e00669. ⟨10.1002/brb3.669⟩. ⟨hal-02083130⟩