GBA2 was first reported in relation to autosomal recessive complex hereditary spastic paraplegia in 2010 (Boukaris et al., PMID: 20593214). The reported phenotypes include cerebellar ataxia, mental impairment (including variable intellectual disability, cognitive decline, and dementia in some patients), and early-onset cataracts.
Eight variants (missense, nonsense, frameshift) that have been reported in 13 probands in 5 publications (PMIDs: 20593214, 23332916, 24252062, 23332917, 24337409) are included in this curation. While additional evidence is available in the literature, the maximum score for genetic evidence (12 points) has been reached. The mechanism of pathogenicity is reported to be loss of function (PMID: 23332916).
In summary, there is definitive evidence supporting the relationship between GBA2 and autosomal recessive complex hereditary spastic paraplegia. This has been repeatedly demonstrated in research and clinical diagnostic settings and upheld over time. This classification was approved by the ClinGen Cerebral Palsy GCEP on May 2, 2024 (SOP Version 10).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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