PMC3681964_01
MRI of the index patient at the age of 54 years.. A. Sagital T1 weighted MRI of the brain showing atrophy of the cerebellar midline, particularly the vermis superior. B&C. Axial T2 weighted MRI showing linear T2 hypointensities in the pons. C. Axial T2 weighted MRI showing prolongation of T2 signal in the dentate nuclei. D. Sagital T2 weighted MRI showing atrophy of the cord, straight dorsal spine and loss of the dorsal kyphosis.
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MRI of the spine showed a straight dorsal spine with loss of the dorsal kyphosis (Figure 1).
PMC3681964_02
PMC3681964_03
Compound heterozygous mutations found in the proband.. Upper part, IGV-browser screenshots of the mutations found by exome sequencing and corresponding Sanger sequencing results. Lower part. Protein multiple sequence alignments (PMSA) of the corresponding residues generated by MUSCLE v3.6 (NCBI HomoloGene) including genes conserved in bony vertebrates (Euteleostomi). Residues in red are predicted to be affected by the mutations found in the proband.
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Two heterozygous mutations were found in the large exon 10 of the SACS gene (NCBI reference sequence NM_014363.4) and these were confirmed by Sanger sequencing (Figure 2). The c.13352T>C is predicted to cause an amino-acid substitution (p.Leu4451Pro) affecting a conserved residue located in the HEPN (Higher Eukaryotes and Prokaryotes Nucleotide-binding) domain (Figure 2).