Ataxia and Weakness in a Young Woman

Figure 1. Magnetic resonance images (MRIs). A, Sagittal T1-weighted brain MRI demonstrating cerebellar atrophy. B, Axial T2-weighted MRI demonstrating normal white matter and subcortical structure. C, Axial T2-weighted MRI demonstrating atrophy of cerebellar hemispheres.

Figure 2. Distribution of pathogenic variants on the hexosaminidase (HEX) A protein for the patient described. The amino acid sequence is represented by a single-letter code, and alternating exons are identified using black and blue fonts. Exon boundaries are marked in red numerals (indicating exon numbers) placed under the sequence. The right column represents the amino acid position. Missense mutation G269S (indicated by S at amino acid position 269 in exon VII) and splice site mutation IVS9 (+1) (represented by Δ at the junction between exons VIII and IX) are marked under the normal sequence. Either of the 2 mutations is expected to lead to protein loss of function. Compound heterozygosity with both mutations located in trans is strongly suspected in this autosomal recessive disorder. The peptide sequence was deduced from reference sequence NM_000520.4 (HEXA gene), analyzed using Ensembl Genome Browser version 66.37 (online resource available at http://useast.ensembl.org/index.html; accessed February 1, 2012).