PMC3281774_01
MRI at age 61 demonstrating severe atrophy of the cerebral hemispheres, cerebellum, and brainstem. A-F: 3-D SPGR coronal MRI; G, H: T1 sagittal MRI; I-L: FLAIR axial MRI, showing white matter signal hyperintensities.
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F1
Brain MRI at that time revealed severe atrophy of the cerebellar hemispheres and vermis, pons, and middle cerebellar peduncles as well as moderate cerebral atrophy; a more recent study at age 61 showed these findings as well as more severe cerebral atrophy (Figure 1).
Results of audiometric testing at age 61 conforming to ANSI 1969 standards. ANSI = American National Standards Institute; dB = decibel; Hz = hertz; PTA = pure tone average.
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F2
Audiometry demonstrated moderate sensorineural hearing loss in the high frequencies on the left, and mild sensorineural hearing loss in the mid-frequencies on the right sloping to a severe loss in the high frequencies (Figure 2).
Results of MitoExome sequencing. Rare, protein-modifying variants were prioritized, revealing a homozygous c.1672C > T (p.R558C) missense mutation in exon 8 of WFS1 that has previously been reported in a patient with Wolfram syndrome.
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F3
Rare, protein-modifying variants found to be homozygous or potentially compound heterozygous were prioritized (Figure 3), revealing an X-linked functional polymorphism c.937G > T (p.D313Y) in GLA that is not considered pathogenic and a homozygous c.1672C > T (p.R558C) missense mutation in exon 8 of WFS1 that has previously been reported in a patient with Wolfram syndrome.