PMC7263430_01
PMC7263430_02
Brain magnetic resonance imaging (MRI). Axial flair sequence MRI at 2 years
(a) and 2 years and 9 months (b): A symmetrical and bilateral high-intensity
signal is observed the periventricular and peritrigonal white matter in addition
to the posterior arm of the internal capsule (red asterisk) and periphery of the
thalamus; the accentuation of the sulci and encephalic cisterns results in
diffuse encephalic reduction and compensatory ectasia of the supra and
infratentorial ventricular system; the diploe is thickened (red arrow), a
finding not observed before, which suggests progressive cerebral atrophy (b).
Axial T2-weighted imaging at 2 years and 9 months (c) demonstrating symmetric
focus with the same CSF sign in the two images in bilateral frontal white
matter, suggesting enlargement of Virchow-Robin spaces, although lesion of
cystic degeneration or encephalomalacia cannot be excluded. Axial T2-weighted
imaging at ages 2 years (d) 2 years and 9 months (e), and coronal T2-weighted
sequences at 2 years and 9 months of age (f): note the symmetrical
high-intensity signal in the cerebellar hemispheres. Axial T2-weighted sequence
at 2 years of age (g) and axial and sagittal T2-weighted imaging at age 2 years
and 9 months (h,i): note the bilateral and symmetrical high-intensity signal of
the substantia nigra of the cerebellar peduncle, mesencephalic segment,
posterior region of the bridge, superior cerebellar peduncle and medulla
oblongata.
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PMC7263430_02_1415-4757-GMB-43-2-e20180271-gf01.jpg
f1
The electroencephalography suggested parieto-occipital epileptiform discharges, and brain magnetic resonance imaging (MRI) showed bilateral high intensity T2/Flair foci in the periventricular and peritrigonal white matter, internal capsule of the posterior limb and thalamus periphery; additionally, hyperintensities were observed in the cerebral peduncle, midbrain tegmentum, dorsal pons, and medulla oblongata, with a few areas of restricted diffusion, which is typical for mitochondrial disorders (Figure 1).
Protein structure and distribution of variants in the
C12orf65 gene. The yellow boxes represent the variants
described in patients with mild phenotypes, the red boxes the variants in
patients with severe phenotype, and the green boxes the variants in patients in
whom it was not possible to classify disease severity based on the available
clinical information. If just one variant is associated with one patient it was
found in the homozygous state; two variants linked to one patient indicates
compound heterozygosis. Patients are numbered as in
.
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PMC7263430_02_1415-4757-GMB-43-2-e20180271-gf02.jpg
f2
The severity of this phenotype can be explained by the variant found, which affects an important functional protein domain (Figure 2). The variants linked to severe phenotypes were more likely to affect the GCQ domain of the protein, although they could impact other protein domains (Figure 2).