The p.A382T TARDBP gene mutation in Sardinian patients affected by Parkinson's disease and other degenerative parkinsonisms.

Based on our previous finding of the p.A382T founder mutation in ALS patients with concomitant parkinsonism in the Sardinian population, we hypothesized that the same variant may underlie Parkinson's disease (PD) and/or other forms of degenerative parkinsonism on this Mediterranean island. We screened a cohort of 611 patients with PD (544 cases) and other forms of degenerative parkinsonism (67 cases) and 604 unrelated controls for the c.1144G > A (p.A382T) missense mutation of the TARDBP gene. The p.A382T mutation was identified in nine patients with parkinsonism. Of these, five (0.9 % of PD patients) presented a typical PD (two with familiar forms), while four patients (6.0 % of all other forms of parkinsonism) presented a peculiar clinical presentation quite different from classical atypical parkinsonism with an overlap of extrapyramidal-pyramidal-cognitive clinical signs. The mutation was found in eight Sardinian controls (1.3 %) consistent with a founder mutation in the island population. Our findings suggest that the clinical presentation of the p.A382T TARDBP gene mutation may include forms of parkinsonism in which the extrapyramidal signs are the crucial core of the disease at onset. These forms can present PSP or CBD-like clinical signs, with bulbar and/or extrabulbar pyramidal signs and cognitive impairment. No evidence of association has been found between TARDBP gene mutation and typical PD.

Compressive behaviour of child and adult cortical bone.

In this study, cortical bone tissue from children was investigated. It is extremely difficult to obtain human child tissue. Therefore, the only possibility was to use bone tissue, free from any lesion, collected from young bone cancer patients. The compressive mechanical behaviour of child bone tissue was compared to the behaviour of adult tissue. Moreover, two hypotheses were tested: 1) that the mechanical behaviour of both groups is correlated to ash density; 2) that yield strain is an invariant. Small parts of the diaphysis of femora or tibiae from 12 children (4-15 years) and 12 adults (22-61 years) were collected. Cylindrical specimens were extracted from the cortical wall along the longitudinal axis of the diaphysis. A total of 107 specimens underwent compressive testing (strain rate: 0.1 s(-1)). Only the specimens showing a regular load-displacement curve (94) were considered valid and thereafter reduced to ash. It was found that the child bone tissue had significant lower compressive Young's modulus (-34%), yield stress (-38%), ultimate stress (-33%) and ash density (-17%) than the adult tissue. Conversely, higher compressive ultimate strain was found in the child group (+24%). Despite specimens extracted from both children and adults, ash density largely described the variation in tissue strength and stiffness (R(2)=in the range of 0.86-0.91). Furthermore, yield strain seemed to be roughly an invariant to subject age and tissue density. These results confirm that the mechanical properties of child cortical bone tissue are different from that of adult tissue. However, such differences are correlated to differences in tissue ash density. In fact, ash density was found to be a good predictor of strength and stiffness, also for cortical bone collected from children. Finally, the present findings support the hypothesis that compressive yield strain is an invariant.