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

• Published in: Brain and behavior 2017-04, Vol.7 (4), p.e00669-n/a
• Main Authors: Tripolszki, Kornélia, Török, Dóra, Goudenège, David, Farkas, Katalin, Sulák, Adrienn, Török, Nóra, Engelhardt, József I., Klivényi, Péter, Procaccio, Vincent, Nagy, Nikoletta, Széll, Márta
• Format: Article
• Language: English
• Subjects: Aged; ALS4; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - genetics; C9orf72 Protein; Deoxyribonucleic acid; DNA; DNA Helicases; Female; Genes; Genomes; Heterozygote; High-Throughput Nucleotide Sequencing; Human health and pathology; Humans; Life Sciences; motor neuron disease; Motor neurone disease; Multifunctional Enzymes; Mutation; Mutation, Missense; Original Research; p.N264S missense mutation; Patients; Phenotype; Proteins; Proteins - genetics; RNA Helicases - genetics; RNA-Binding Protein FUS - genetics; SETX gene; targeted sequencing
• ISSN: 2162-3279; 2162-3279
• DOI: 10.1002/brb3.669

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: FUS, SETX, and C9ORF72. Results A novel heterozygous missense mutation (c.791A>G, p.N264S) of the SETX 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. Targeted next‐generation sequencing identified a novel heterozygous missense mutation (c.791A>G, p.N264S) of the SETX gene in a Hungarian ALS patient with an unusual phenotype.