An Original Target Genetic Panel to Diagnose Neurodegenerative Diseases on the Basis of Next-Generation Sequencing: First Experience

The aim of the study was to assess the efficacy of a diagnostic panel based on next-generation sequencing (NGS) and developed by our team, to diagnose a wide range of socially significant hereditary degenerative diseases of the brain.

Materials and Methods. Using the diagnostic target NGS panel (powered by Illumina MiSeq, USA), designed to sequence the encoding area of 300 genes related to neurodegenerative diseases manifesting with movement and cognitive disorders, we performed a mutation screening of the DNA of 32 patients with an otherwise obscure diagnosis.

Results. The application of the original genetic panel revealed a number of rare hereditary neurodegenerative pathologies with mutations in genes for spinocerebellar ataxias and paraplegias, parkinsonism, dystonias, and neurometabolic diseases, identified by NGS and confirmed by direct sequencing. In 11 patients, 12 mutations were found in 10 different genes, causing the development of three autosomal recessive diseases (genes DDHD1, NPC1 and RARS) and eight diseases associated with autosomal dominant inheritance (genes SPAST, SPTBN2, GRN, GCH1, LRRK2, NOTCH3 and AGER).

Conclusion. Panel screening of uncertain cases of neurodegenerative diseases using this bespoke target model enabled us to reveal and subsequently confirm mutations in various genes for more than a quarter of the examined patients.

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