Recently, p.N352S mutation in TARDBP was first identified in

a German family by Kühnlein et al [5] (Table 2). Their case showed fine motor skill impairments of the right hand selleck chemical as the first sign at the age of 40 years. In this pedigree, the patient’s aunt with onset in the distal upper extremity and a distant female relative with onset in the right distal upper extremity were also affected by the motor neurone disease. Kamada et al. [1] reported the same mutation in one of 30 Japanese patients with SOD1-negative FALS (Table 2). Their case exhibited weakness of the right hand as the first sign at the age of 55 years. Although the clinical features have not been described, five families with FALS with p.N352S mutation in TARDBP, including 15 cases diagnosed with FALS and three cases diagnosed with sporadic

ALS, have been reported [11]. p.N352S mutation in TARDBP have been reported in two cases with motor neurone disease who were clinically diagnosed with progressive muscular learn more atrophy [10] (Table 2) whose onset sites and ages were cervical at 68 years and lumbosacral at 61 years, respectively. Our case exhibited upper extremity impairment at onset similar to the previously reported cases of FALS with p.N352S mutation in TARDBP. Furthermore, all reported cases with p.N352S mutation in TARDBP, including our case, showed LMN signs with no detectable UMN and no cognitive impairment (Table 2). Their duration of illness was at least 4 years. Among the clinical features, the major symptoms of this FALS mutation type seemed to be as follows: (i) a tendency for onset in the upper extremities;

(ii) presence of LMN signs and no detectable UMN sign; (iii) no cognitive impairments; and (iv) a relatively long prognosis. The clinicopathological features of autopsy-confirmed FALS cases with several TARDBP mutations have been described (Table 2) [6–9]. Their sites of onset were variable, and most had both UMN and LMN signs during the disease course. Cognitive impairment was not observed in all cases, which was similar to those with p.N352S mutation in TARDBP. Thus, although the clinical features of several types of TDP-43-mutated FALS 4-Aminobutyrate aminotransferase seem to vary, none of them was affected by cognitive impairment (Table 2). As described in the Table 2, the previously reported cases of autopsy-confirmed FALS with TARDBP mutations [6–9] exhibited several common neuropathological features, including (i) degeneration of both the UMN and LMN systems; (ii) presence of Bunina bodies; and (iii) widespread TDP-43-immunopositive NCIs and GCIs. Similar to the previously reported FALS cases with TARDBP mutations, our present case showed LMN system degeneration with Bunina bodies, suggesting the possible presence of TARDBP mutations in several sporadic ALS cases.