{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pauly MG"],"funding":["Damp Foundation","German Research Foundation","Deutsche Forschungsgemeinschaft","Medical Research Council","European Union Seventh Framework Programme","European Union’s Horizon 2020","“Gutes tun”"],"pagination":["1874"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9953040"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["24(3)"],"pubmed_abstract":["<i>VPS13D</i> is one of four human homologs of the <i>vacuolar sorting protein 13</i> gene (<i>VPS13</i>). Biallelic pathogenic variants in the gene are associated with spastic ataxia or spastic paraplegia. Here, we report two patients with intronic pathogenic variants: one patient with early onset severe spastic ataxia and debilitating tremor, which is compound-heterozygous for a canonical (NM_018156.4: c.2237-1G > A) and a non-canonical (NM_018156.4: c.941+3G>A) splice site variant. The second patient carries the same non-canonical splice site variant in the homozygous state and is affected by late-onset spastic paraplegia. We confirmed altered splicing as a result of the intronic variants and demonstrated disturbed mitochondrial integrity. Notably, tremor in the first patient improved s"],"journal":["International journal of molecular sciences"],"pubmed_title":["Not to Miss: Intronic Variants, Treatment, and Review of the Phenotypic Spectrum in <i>VPS13D</i>-Related Disorder."],"pmcid":["PMC9953040"],"funding_grant_id":["DFG-GEPRIS 413535489","469177153","779257","305444","MR/S005021/1′","MR/S005021/1","n. a.","BR4328.2-1"],"pubmed_authors":["Grozinger A","Houlden H","Lohmann K","Pauly MG","Turchetti V","Munchau A","Bruggemann N","Tadic V","Efthymiou S","Diaw SH","Vona B","Chelban V"],"additional_accession":[]},"is_claimable":false,"name":"Not to Miss: Intronic Variants, Treatment, and Review of the Phenotypic Spectrum in <i>VPS13D</i>-Related Disorder.","description":"<i>VPS13D</i> is one of four human homologs of the <i>vacuolar sorting protein 13</i> gene (<i>VPS13</i>). Biallelic pathogenic variants in the gene are associated with spastic ataxia or spastic paraplegia. Here, we report two patients with intronic pathogenic variants: one patient with early onset severe spastic ataxia and debilitating tremor, which is compound-heterozygous for a canonical (NM_018156.4: c.2237-1G > A) and a non-canonical (NM_018156.4: c.941+3G>A) splice site variant. The second patient carries the same non-canonical splice site variant in the homozygous state and is affected by late-onset spastic paraplegia. We confirmed altered splicing as a result of the intronic variants and demonstrated disturbed mitochondrial integrity. Notably, tremor in the first patient improved s","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2025-04-21T17:25:31.151Z","creation":"2024-12-04T12:38:33.142Z"},"accession":"S-EPMC9953040","cross_references":{"pubmed":["36768210"],"doi":["10.3390/ijms24031874"]}}