Fig 1.
The figure explains the selection of probands from the clinicogenetic database, and the resulting total number of molecular diagnoses. VUS: variants of uncertain significance. * Indicates selection criteria of 105 probands: 1) Verified family history; 2) Completed thorough investigations; 3) Availability of probands; 4) Sporadic cases considered to be HSP or HA, fulfilling 2) and 3).
Table 1.
Clinical characteristics of the 105 probands included in the study.
Table 2.
Pathogenic and likely-pathogenic variants identified in hereditary ataxia and spastic paraplegia probands.
Table 3.
List of variants of uncertain significance.
Table 4.
Clinical features of the probands with definitive molecular diagnosis having pathogenic and likely-pathogenic variants.
Fig 2.
Pedigree structures of families with KIF1A variants.
(a) Pedigree structure of family HCT-024 (III-7) with a c.80T>C, p.(Ile27Thr) variant in KIF1A. The filled symbols indicate affected individuals. The striped symbol indicates an individual that was initially classified as a non-affected individual, but after clinical re-examination was also found to be possibly affected. (b) Pedigree structure of family of HCT-026 (IV-6) with a c.22G>A, p.(Val8Met) variant. The symbols with a question mark are not confirmed regarding the phenotype. The diamond shaped symbols indicate masked gender. A line crossing a symbol represents a deceased individual. Probands are labelled with ‘P’.
Fig 3.
Pedigree structure and MRI scans of a family with SACS variants.
(a) Pedigree structure of family HCT-106 (V-3) with a c.12688G>A, p.(Gly4230Ser) and c.12661C>G, p.(Leu4221Val) variants in SACS. A consanguineous marriage between individuals IV-2 and III-4 is indicated by a double line. Cerebral MRIs of HCT-106 at disease duration of 28 years in (b) FLAIR sequence in midline sagittal plane, (c) FLAIR sequence in coronal plane at the level of dorsal aspect of cerebellum, (d) FLAIR sequence in transversal plane at the level of the middle cerebellar peduncles, and (e) T2 sequence in transversal plane at the level of the superior cerebellar peduncles, showing atrophy of the cerebellar hemispheres and vermis with widening of fissures and folia.