Hereditary Spastic Paraplegia - adult onset

Gene: UBAP1

Green List (high evidence)

Five unrelated families reported with childhood-onset HSP. A recurrent two‐base pair deletion (c.426_427delGA, p.K143Sfs*15) in the UBAP1 gene was found in four families, and a similar variant (c.475_476delTT, p.F159*) was detected in a fifth family. The variant was confirmed to be de novo in two families and inherited from an affected parent in two other families. RNA studies performed in lymphocytes from one patient with the de novo c.426_427delGA variant demonstrated escape of nonsense‐mediated decay of the UBAP1 mutant transcript, suggesting the generation of a truncated protein. Both variants identified are predicted to result in truncated proteins losing the capacity of binding to ubiquitinated proteins, hence appearing to exhibit a dominant‐negative effect on the normal function of the endosome‐specific endosomal sorting complexes required for the transport‐I complex.

PMID 32934340: additional 7 families. Median age of onset 10yrs.
Sources: Literature

Created: 22 Apr 2020, 4:17 a.m. | Last Modified: 16 Mar 2021, 9:17 a.m.

Panel Version: 0.110

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Childhood-onset hereditary spastic paraplegia; Spastic paraplegia 80, autosomal dominant 618418

Publications

• 31696996
• 32934340

Mode of pathogenicity
Other