Association between Hereditary Spastic Paraplegia and a Novel SPAST Exon 11 Mutation

Abstract

Background: Hereditary spastic paraplegias (HSPs) are a heterogeneous and rare group of neurodegenerative disorders characterized by gradually progressing spasticity and weakness in the lower limbs. Various genes are associated with both the pure and the complex types of hereditary spastic paraplegia (HSP). Methods: In this study, next-generation sequencing was employed to explore the case of a male proband suffering from HSP who has been unable to stand or walk since childhood due to an abnormal gait. A thorough examination was conducted, and the sequence data from both the proband and his parents were analyzed. Adhering to the guidelines set by the American College of Medical Genetics and Genomics (ACMG), these data were processed using the Online Mendelian Inheritance in Man (OMIM) database, as well as other resources such as The Human Phenotype Ontology (HPO), Chinese Human Phenotype Ontology (CHPO), and Orphanet. Results: The cause of HSP in the proband was identified as a novel Exon 11 mutation detected at c.1131A>C (p.Asp444Ala). This mutation was determined to be a pathogenic gene and de novo, with no family history of the disorder. Conclusions: This study aimed to uncover a novel genetic basis for HSP and advocate for Spastin (SPAST) testing among patients with the disorder. This research contributes to the understanding and expansion of the phenotype spectrum of SPAST-related diseases.