We have shown that the cases with GRIM-19 mutations display increased expression of the STAT3 regulated gene ICAM1; this finding fits with a loss of function of GRIM-19.
In support of this hypothesis, postmortem brain sections from the motor cortex of ALS patients harboring either FUS R521C or P525L mutations display increased levels of the γH2AX DNA damage marker relative to control brain sections (W. Y. Wang et al., 2013).
These findings basically mirror the results of our biomechanical analysis of primary myoblasts derived from a patient with a heterozygous R350P desmin mutation, which displayed increased cell stiffness and a higher rate of cell death and substrate detachment [ 6].
Strikingly, ZnT3 harboring the Y357F mutation behaved as a "gain-of-function" mutant as it displayed increased ZnT3 oligomerization, targeting to SLMVs, and increased resistance to zinc toxicity.
Loss-of-function mutations in several Imd pathway genes displayed increased sensitivity to CrPV infection and higher CrPV loads.
Our results are in agreement with a recently published study reporting that FAP patients with heterozygous mutation in the APC gene also displayed increased mean BMD [16].
Specifically, motor neurons expressing G93A hSOD1 mutations, which have been linked to familial ALS, displayed increased calcium uptake by SERCA receptors coupled with alterations in mitochondrial calcium efflux.
By contrast, the point mutation in the conserved aspartate residue of motif II (D279A), which abrogates ATP hydrolysis, displayed increased binding to mRNA.
Similar to the effect on CG6770 and cabut, TOR-mutant larvae displayed increased d4E-BP transcription, which was completely suppressed by the fkh1 or the fkh6 mutation (Figure 7B).
Further, since mutations at N105 and A206 were previously shown to have no effect on folding kinetics, we wondered if these variants displayed increased resistance to chemical denaturation [7].
