biostudies-literaturePauly MGDamp FoundationGerman Research FoundationDeutsche ForschungsgemeinschaftMedical Research CouncilEuropean Union Seventh Framework ProgrammeEuropean Union’s Horizon 2020“Gutes tun”1874https://www.ebi.ac.uk/biostudies/studies/S-EPMC9953040biostudies-literatureUnknown24(3)<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 sInternational journal of molecular sciencesNot to Miss: Intronic Variants, Treatment, and Review of the Phenotypic Spectrum in <i>VPS13D</i>-Related Disorder.PMC9953040DFG-GEPRIS 413535489469177153779257305444MR/S005021/1′MR/S005021/1n. a.BR4328.2-1Grozinger AHoulden HLohmann KPauly MGTurchetti VMunchau ABruggemann NTadic VEfthymiou SDiaw SHVona BChelban VfalseNot to Miss: Intronic Variants, Treatment, and Review of the Phenotypic Spectrum in <i>VPS13D</i>-Related Disorder.<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 s2023-01-01T00:00:00Z2023 Jan2025-04-21T17:25:31.151Z2024-12-04T12:38:33.142ZS-EPMC99530403676821010.3390/ijms24031874