The homology structure model of TIL domain of the wild-type and mutated form of BmSPI39 showed that two cysteine mutations may cause incorrect disulfide bond formation of B. mori TIL-type protease inhibitors.
These findings suggest that the PD-linked mutations may cause neurodegeneration via different mechanisms, some of which may be independent of α-Syn aggregation.
We postulate that these mutations may cause neurotoxicity via two distinct pathways, changes in actin dynamics (G- to F-actin polymerization) and cellular signaling pathways (e.g., PIP2 pathway), via PLP-binding and interactions that require further study.
Point, deletion, and insertion mutations may cause an abnormal protein to be synthesized or may prevent the protein from being made at all.
The first common functional trait identified so far, in four of these mutants, is an increased sensitivity to the acetylcholine, suggesting that these mutations may cause a gain of function.
Studies of null Slc26a6−/− mice have shown a phenotype of hyperoxaluria, hyperoxalemia, and calcium oxalate urolithiasis, leading to the hypothesis that SLC26A6 mutations may cause or modify hyperoxaluria in humans.
In the cases of mutations affecting rod-specific genes such as rhodopsin, it is unclear how the mutations may cause degeneration of cones.
These findings indicate that PTRF mutations may cause LQTS and life-threatening arrhythmias; thus, it is necessary to take precautionary measures in these patients.
The process of reverse transcription is extremely error-prone, and the resulting mutations may cause drug resistance or allow the virus to evade the body's immune system.
Apart from MADH4, it is not clear whether mutations in ENG and ACVRL1 lead to particular symptoms, although some reports suggest that ENG mutations are more likely to cause lung problems while ACVRL1 mutations may cause more liver problems, and pulmonary hypertension may be a particular problem in people with ACVRL1 mutations.
