USP8 variants as a cause of Hereditary spastic paraplegias: Case report

Introduction: Hereditary spastic paraplegias (HSP) are a group of rare neurodegenerative diseases with different modes of inheritance. HSP is both clinically and genetically a heterogeneous disorder and it is characterized by progressive degeneration which leads to lower limb spasticity and weakness. Based on the clinical phenotypes, this disorder is classified to two main types naming pure and complex Pure HSP is characterized by insidiously progressive weakness and complex form may be combined with other neurological and non-neurological clinical features. This additional manifestations including such as cognitive impairment, ataxia, dysarthria, neuropathy, or seizures. Based on previous studies 79 genes involved in HSP with all patterns of inheritance have been described. We describe a 7-year-old HSP affected daughter and her family both clinically and geneticallyMaterials & Methods: A girl born to a consanguineous parent, referred to pediatric neurologist when she was 7-yearold because of Ataxi, walking imbalance and hearing loss. She had also one brother with similar symptoms such as hearing impairment and two times experienced heart failure.WES and direct sequencing was conducted in order to find any alterationsResults: Genetic analysis and direct sequencing of exon15 of USP8 gene revealed a heterozygous variant at position c.2371A> G (p. Ile791Val) which was not previously categorized as a pathogenic mutation. Further In-silico investigations by Mutation Taster predicted this variant as a pathogenic one. This alteration was confirmed in all three members of this familyConclusion & discussion: Our results further suggest that USP8 should be investigated in more HSP affected patients and based on the results of the frequency of this mutation, it can be concluded in screening panels, particularly for genetically undiagnosed HSP patients.

Keywords:

Hereditary spastic paraplegias , neurodegenerative diseases , USP8 , Genetic analysis