Application of a custom NGS gene panel revealed a high diagnostic utility for molecular testing of hereditary ataxias
| Autor: | Ewelina Elert-Dobkowska, Aleksandra Klimkowicz-Mrowiec, Karolina Ziora-Jakutowicz, Iwona Stepniak, Wiktoria Radziwonik, Jacek Zaremba, Anna Sulek |
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| Rok vydání: | 2021 |
| Předmět: |
Spastin
Spastic Paraplegia Hereditary Ubiquitin-Protein Ligases DNA Helicases High-Throughput Nucleotide Sequencing Computational biology General Medicine Biology Multifunctional Enzymes Hereditary Ataxias Molecular Diagnostic Techniques Muscle Spasticity Gene panel Mutation Genetics Humans Spinocerebellar Ataxias Ataxia RNA Helicases Spinocerebellar Degenerations |
| Zdroj: | Journal of applied genetics. 63(3) |
| ISSN: | 2190-3883 |
| Popis: | Background Hereditary ataxias (HA) are a rare group of heterogeneous disorders. Here, we present results of molecular testing a group of ataxia patients using custom-designed Next Generation Sequencing (NGS) panel. Due to genetic and clinical overlapping of hereditary ataxias and spastic paraplegias (HSP), designed panel encompassing together HA and HSP genes. Methods The NGS libraries comprising coding sequence for 152 genes were performed using KAPA HyperPlus and HyperCap Target Enrichment Kit and sequenced on the MiSeq instrument. Obtained results were analyzed using BaseSpace Variant Interpreter and Integrative Genomics Viewer. All pathogenic and likely pathogenic variants were confirmed using the Sanger sequencing. Results A total of 29 patients with hereditary ataxias were enrolled to the NGS testing, and 16 patients had a confirmed molecular diagnosis with diagnostic efficiency of 55.2%. Pathogenic or likely pathogenic mutations were identified in 10 different genes: POLG (PEOA1, n=3; SCAE, n=2), CACNA1A (EA2, n=2), SACS (ARSACS, n=2), SLC33A1 (SPG42, n=2), STUB1 (SCA48, n=1), SPTBN2 (SCA5, n=1), TGM6 (SCA35, n=1), SETX (AOA2, n=1), ANO10 (SCAR10, n=1), SPAST (SPG4, n=1). Conclusions We demonstrated that approach based on targeted NGS panel can be highly effective and useful tool in the molecular diagnosis of ataxia patients. Furthermore, we highlight that sequencing panel targeted to ataxias together with HSP genes increase the diagnostic success. |
| Databáze: | OpenAIRE |
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