Figure 1

Pedigrees and CT-scans of patients harboring XPR1/SLC53A1 variants located outside of the SPX-encoding domain. (a) Reduced pedigrees of the probands harboring XPR1/SLC53A1 variants. Open symbol: unaffected; filled symbol: affected (presence of brain calcifications); symbol with a diagonal line: deceased; arrow: proband; numbers in parentheses: age at death; Star: DNA available; WT: wild type. (b) CT scans of the probands in axial sections, arrows indicate the different areas of calcifications; Le: Lenticular; T: Thalamic; SCWM: Subcortical white matter; CbH: Cerebellar hemisphere; Ve: Vermis; Midb: Midbrain. (c) Schematic representation of the XPR1/SLC53A1 gene with the SPX-encoding exons indicated in orange, with the changes corresponding to the three PFBC variants indicated on exons 11 and 14 (arrows). (d) Schematic representation of the XPR1 protein structure with the SPX domain highlighted in orange, and the three residues corresponding to the two XPR1/SLC53A1 variants p.(R459C and pN619D) and the de novo mutant (pI629S) shown in green. The topological structure was generated using Protter program³⁹. (e) Alignment of XPR1 orthologs, exclusively from metazoan species, showing the evolutionary conservation of the regions wherein PFBC variants were located.