PMC6276426_01
Brain MRI of the patients V.1 ((a) and (b)) and V.2 ((c) and (d)). (a) Coronal T2 weighted image showing enlargement of the cortical furrows and the ventricular cavities related to a diffuse cortical and subcortical atrophy. (b) Axial T2 weighted sequence showing the huge cortical and subcortical atrophy. (c) T2 weighted sequence shows dilatation in all ventricular cavities as a result to a diffuse and severe atrophy in the brainstem and the cerebellar and the sustentorial area. (d) T2 weighted sequence showing a major ventricular dilatation due to the severe cortical atrophy.
CRIG2018-8635698.002.jpg
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fig2
Brain-MRI showed an important ventricular dilatation due to the diffuse homogenous atrophy of the sustentorial structures and the brainstem (Figures 2(c) and 2(d)).
PMC6276426_02
Brain MRI of the patients V.1 ((a) and (b)) and V.2 ((c) and (d)). (a) Coronal T2 weighted image showing enlargement of the cortical furrows and the ventricular cavities related to a diffuse cortical and subcortical atrophy. (b) Axial T2 weighted sequence showing the huge cortical and subcortical atrophy. (c) T2 weighted sequence shows dilatation in all ventricular cavities as a result to a diffuse and severe atrophy in the brainstem and the cerebellar and the sustentorial area. (d) T2 weighted sequence showing a major ventricular dilatation due to the severe cortical atrophy.
CRIG2018-8635698.002.jpg
PMC6276426_02_CRIG2018-8635698.002.jpg
fig2
Brain-MRI showed an important ventricular dilatation due to the diffuse homogenous atrophy of the sustentorial structures and the brainstem (Figures 2(c) and 2(d)).
Plot of whole genome linkage analysis. Parametric multipoint LOD scores indicate linkage to three loci on 3p24.1-22.2, 13q33.2-34, and 15q22.2-25.1 with a maximum LOD score close to three.
CRIG2018-8635698.003.jpg
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fig3
Whole genome LOD score analysis under the assumption of full penetrance and a disease allele frequency of 0.001 revealed a significant LOD score over 2.9 on chromosomes 3p24.1-22.2, 13q33.2-34, and 15q22.2-25.1 (Figure 3).
Pipeline for filtration of the damaging variants.
CRIG2018-8635698.004.jpg
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fig4
These mutations were subsequently filtered according to the criterion of the frequency of the minor allele less than 5% that yielded 1919 low frequency variants (LFV, MAF < 5%) in 1826 genes (Figure 4).
Sanger sequencing plot of GLB1 showing the p.Arg201Cys mutation at heterozygous state in the father IV.1, the mother IV.2, and her sister IV.3 (a) and at homozygous state in patients V.1, V.2, and V.3 (b). EXOSC8 p.Ser272Thr mutation at heterozygous state found in patients V.1, V.2, and V.3, theirs mother IV.2, and their aunt IV.3 (c). Arrows indicate mutation positions.
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fig5
The three patients were homozygous and the parents were heterozygous for the mutation (Figures 5(a) and 5(b)). Sanger sequencing found this mutation at heterozygous state in all the patients, their mother, and their aunt (Figure 5(c)).