Fig. 1

Pedigree, genetic and brain MRI features of the index SCA48 family with the novel STUB1 frameshift mutation. A Pedigree of the index family with the heterozygous rare frameshift variant, c.832del (p.Glu278fs), in the STUB1 gene. m/wt = heterozygous carriers of the STUB1 mutation; wt/wt = non-carriers; open symbols = unaffected; filled symbols = affected; symbol with a diagonal line = deceased; arrow = proband. Asterisks indicate family members whose whole genomes were sequenced. B Sanger sequencing traces confirming the c.832del (p.Glu278fs) variant in STUB1 identified in the proband and affected members of the index family. C Brain MRI scans show cerebellar atrophy (arrows) with preserved pons (asterisk) in patients III:1 and III:2 of the index family, and an age- and gender-matched healthy control participant. D CHIP comprises three functional domains: TPR, coiled-coil, and U-Box. The protein structure shows that the p.Glu278fs variant amino acid residue (red) is located in the U-Box domain of CHIP. The CHIP Δ278–303 mutation results in a truncated protein without the C-terminal 22 aa of the U-box domain (278–303). A sequence alignment (top) demonstrates the evolutionary conservation of E278 in the U-Box domain of CHIP proteins across the indicated species. Identical residues are labeled in yellow