PMC5121365_01
MRI showing brain anomalies, sequence analysis and protein structure prediction of PDHA1 with c.523G > A (p.A175T) mutation in our patient. A. Brain MRI with and without contrast of our patient at 27 months of age: T2 sagittal image showing severely hypoplastic corpus callosum (arrowhead) (A-i); T2 and T1 axial images, respectively, showing marked ventriculomegaly (arrowhead) and marked loss of volume of the brain parenchyma with marked prominence of the cortical sulci (arrow) (A-ii and iii); and T1 axial image showing a component of cerebellar vermian hypoplasia (arrowhead), consistent with Dandy-Walker variant (A-iv). No abnormalities noted in the basal ganglia and there was absence of the cavum septum pellucidum (not shown here). B. Sequence chromatograms of PDHA1 showing a normal sequence in the proband's mother's blood (B-i); mosaicism for c.523G > A (p.A175T) in the proband's cultured SFs (B-ii); the proband's blood (B-iii); and the proband's buccal cells (B-iv). Note the difference in mosaic ratio among samples; the peak heights vary in forward and reverse sequences and are not quantitative. C.In silico prediction of altered protein structure of PDHA1 c.523G > A (p.A175T) mutation (red) based on Protein Data Bank entry 3EXE (Swiss-pdbViewer 4.1.0, http://spdbv.vital-it.ch). Side-chains and polypeptide backbone of E1alpha and E1beta are depicted in yellow and blue, respectively. Hydrogen bonds are shown in green.
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Repeat brain MRI at two years of age revealed severe hypoplasia of the corpus callosum, ventriculomegaly, hypoplasia of the cerebellar vermis consistent with the Dandy Walker variant, marked volume loss of the brain parenchyma and prominence of the cortical sulci, and absence of the cavum septum pellucidum (Fig. 1A).