Neuroimaging findings.

<p>A: axial T2 weighted MRI of patient 2 taken during an episode with seizures, increasing encephalopathy and exacerbation of the dystonia. Images show bilateral high T2-signal changes and swelling in the putamen and caudate head. In addition there are multiple cortical lesions preferentially occurring in the depths of sulci, which is typical of BBGD. B: axial T2 and coronal T2-FLAIR weighted MRI of patient 1 taken during an episodic exacerbation show a similar pattern with bilateral striatal and multiple cortical lesions. The signal abnormalities regressed completely on later scans (not shown). C (upper lane): FDG-PET scan of the brain of patient 1 taken ~5 years later shows multiple foci of decreased glucose metabolism that correlate to the localization of the transient cortical signal changes on MRI. The striatum shows minimal uptake consistent with severe neuronal loss. A normal scan is shown in the lower lane for comparison.</p

Genetic and molecular findings.

<p>A: coverage analysis of whole-genome sequencing data in patient 3 shows a clear regional drop in sequencing depth (red line) corresponding to the 45,049 bp deletion in the 5’-UTR of the <i>SLC19A3</i> gene. The two arrows mark the position of the break-points. Coverage in the same region of a control is shown in the bottom lane for comparison. The blue diagram depicts the SLC19A3 gene in a 3’-5’ alignment. Vertical rectangulars show the proportional position of the exons. B: Western blot analysis in frontal cortex homogenate of patient 1 using two primary antibodies (left and right panel) shows an increase of SLC19A3 protein immunoreactivity in the patient (P) compared to two age and gender matched controls (C1, C2).</p

Pedigrees with homozygous c.1528_1529del [p.Met510Valfs*17] <i>GBA2</i> mutation

<p>A) Kindred 66 was originally reported by Skre and Berg [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0169309#pone.0169309.ref013" target="_blank">13</a>]. Arrow: probands; Squares: males; circles: females; diagonal line: deceased individual; Black symbols: affected individuals; white symbols: unaffected individuals; w/w: homozygous for the wild-type allele; w/m: heterozygous for the <i>GBA2</i> c.1528_1529del mutation; m/m: homozygous for the <i>GBA2</i> c.1528_1529del mutation. B) Sequencing of the <i>GBA2</i> transcript. Sequencing of the GBA2 transcript using RNA purified from cultured patient fibroblasts showed homozygosity for the 2 bp deletion (c.1528_1529del).</p

Clinical features of patients harbouring the homozygous c.1528_1529del [p.Met510Valfs*17] GBA2 mutation.

<p>Clinical features of patients harbouring the homozygous c.1528_1529del [p.Met510Valfs*17] GBA2 mutation.</p