A patient carrying a homozygous p.A382T TARDBP missense mutation shows a syndrome including ALS, extrapyramidal symptoms, and FTD

Abstract

We have recently published data showing that a founder mutation of the TARDBP gene (p.A382T) accounts for approximately one third of amyotrophic lateral sclerosis (ALS) cases on the Mediterranean island of Sardinia (Chiò et al., 2011). In that report, we identified a 53-year-old man carrying a homozygous A382T missense mutation of the TARDBP gene with a complex neurological syndrome including amyotrophic lateral sclerosis, parkinsonian features, motor and vocal tics, and frontotemporal dementia (FTD). Due to the uniqueness of this case, here we provide a detailed clinical description, as well as neurophysiological, neuropsychological, and neuroimaging data for that case and his extended family.

Figure 1

Family pedigree. Square indicates male; circle, female; slash, deceased; and arrow, index patient. The red square indicates ALS; the blue square, vocal and motor tics; the yellow square, FTD; the green square, parkinsonism; and the violet point, tremor.

Figure 2

(A) Perfusion SPECT with ⁹⁹Tc-ECD (ethylene cystine dimer), patient III-1. The transversal scans show a marked reduction of the uptake in the frontotemporal regions bilaterally and in the right parietal lobe. (B) The patient’s SPECT is compared to a that of a normal subject with the same age as patient III-1.

Figure 3

(A) ¹⁸F-FDG PET scan, patient III-1. The sagittal scans show the reduction of the ¹⁸F-FDG uptake on the right frontal precentral gyrus, on the right and left parietal postcentral gyrus and on the right insula. (B) ¹⁸F-FDG PET scan of a normal subject with the same age as patient III-1.