The Application of Massively Parallel Next Generation Sequencing Technologies for Diagnosis of Hereditary Spastic Paraplegia: A Contribution to the Development of DNA Diagnosis of a Highly Heterogeneous Disease

Doctoral thesis Anna Uhrová Mészárosová, MSc. The Application of Massively Parallel Next Generation Sequencing Technologies for Diagnosis of Hereditary Spastic Paraplegia: A Contribution to the Development of DNA Diagnosis of a Highly Heterogeneous Disease. Prague, 2018 Abstract The aim of this work is to map the genetical spectrum of hereditary spastic paraplegia in Czech patients. Hereditary spastic paraplegia (HSP) is an inherited neurological disorder, clinically characterized by progressive weakness and spasticity of the lower limbs leading to problems with gait and can cause the complete loss of the ability to walk. HSP is clinically and genetically very heterogenous; more than 90 HSP types and pathogenic variants in more than 70 genes have been described to date. HSP manifests as an uncomplicated (pure) form in the majority of HSP patients. Less often it manifests as a complicated phenotype with the associated clinical signs (mental impairment, epilepsy, ataxia, atrophy of the optic nerve). We performed massively parallel sequencing (MPS) of uncomplicated HSP gene panel in a group of 96 Czech patients with suspected uncomplicated type of HSP. In all patients the most common HSP type SPG4 was previously excluded. HaloPlex Target Enrichment kit and SureSelect Target Enrichment kit (both Agilent..