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Two novel truncating variants in UBAP1 are responsible for hereditary spastic paraplegia.

ABSTRACT: Hereditary spastic paraplegias (HSPs) are a group of rare neurodegenerative disorders. HSPs are complex disorders and are clinically and genetically heterogeneous. To date, more than 80 genes or genetic loci have been reported to be responsible for HSPs in a Mendelian-dependent manner. Most recently, ubiquitin-associated protein 1 (UBAP1) has been recognized to be involved in HSP. Here, we identified novel protein truncating variants in two families with pure form of HSP. A novel deletion (c.468_469delTG) in the UBAP1 gene was found in the first family, whereas a nonsense variant (c.512T>G) was ascertained in the second family. The variants were confirmed in all patients but were not detected in unaffected family members. The mutations resulted in truncated proteins of UBAP1. The variants did not result in different subcellular localizations in neuro-2a cells. However, each of the two variants impaired neurite outgrowth. Taken together, our findings expand the pathogenic spectrum of UBAP1 variants in HSP.

SUBMITTER: Bian X

PROVIDER: S-EPMC8244911 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Truncating Mutations in UBAP1 Cause Hereditary Spastic Paraplegia.

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A novel truncating variant of <i>SPAST</i> associated with hereditary spastic paraplegia indicates a haploinsufficiency pathogenic mechanism.

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Project description:GENOME STUDIES IN HEREDITARY SPASTIC PARAPLEGIA

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