Mutational Spectrum of Spast (Spg4) and Atl1 (Spg3a) Genes In Russian Patients With Hereditary Spastic Paraplegia
| Autor: | G. E. Rudenskaya, A. A. Stepanova, O. P. Ryzhkova, V. A. Kadnikova, I. G. Sermyagina |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Proband
Adult Male Spastin Genotype Adolescent Hereditary spastic paraplegia lcsh:Medicine Biology DNA sequencing Article Russia Exon symbols.namesake Young Adult GTP-Binding Proteins medicine Missense mutation Humans Genetic Predisposition to Disease Multiplex ligation-dependent probe amplification Motor neuron disease lcsh:Science Child Gene Aged Sanger sequencing Genetics Motor Neurons Multidisciplinary Spastic Paraplegia Hereditary lcsh:R High-Throughput Nucleotide Sequencing Membrane Proteins Exons Middle Aged medicine.disease Pedigree Child Preschool Mutation symbols Next-generation sequencing lcsh:Q Female |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-8 (2019) |
| ISSN: | 2045-2322 |
| Popis: | Hereditary spastic paraplegia (HSP) comprises a heterogeneous group of neurodegenerative disorders, it share common symptom - of progressive lower spastic paraparesis. The most common autosomal dominant (AD) forms of HSP are SPG4 (SPAST gene) and SPG3 (ATL1 gene). In the current research we investigated for the first time the distribution of pathogenic mutations in SPAST and ATL1 genes within a large cohort of Russian HSP patients (122 probands; 69 famillial cases). We determined the frequencies of genetic abnormalities using Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and Next Generation Sequencing (NGS) of targeted gene panels. As a result, SPG4 was diagnosed in 30.3% (37/122) of HSP cases, where the familial cases represented 37.7% (26/69) of SPG4. In total 31 pathogenic and likely pathogenic variants were detected in SPAST, with 14 new mutations. Among all detected SPAST variants, 29% were gross deletions and duplications. The proportion of SPG3 variants in Russian cohort was 8.2% (10/122) that were all familial cases. All 10 detected ATL1 mutations were missense substitutions, most of which were in the mutational hot spots of 4, 7, 8, 12 exons, with 2 novel mutations. This work will be helpful for the populational genetics of HSP understanding. |
| Databáze: | OpenAIRE |
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