Therefore, it is hypothesized that the mutations in DFNA5 might function on both of sensorineural hearing loss and carcinogenesis through activating the apoptosis [ 24].
Despite the apparent importance of the endosomal sorting pathway in CMT and mechanistic commonalities, it should be noted that some of these mutations cause demyelinating neuropathies and might function in Schwann cells (SH3TC2, SIMPLE), whereas others cause axonal neuropathies and might function in neurons (RAB7, FIG4).
To understand how the E104 mutation might affect Cdc8p function, we considered Myo52, a myosin V-class myosin that is involved in vesicular and organelle transport in cells (Hammer and Sellers, 2012).
As this domain is located in the TACC domain, the L461A mutation might also abrogate the function of Alp7.
Prior studies did not clearly predict the effects a hif-1 loss-of-function mutation might have on longevity.
If such a substitution sufficiently impairs the AR DNA interaction [33], this loss-of-function mutation might explain the apparent lack of AR responsiveness observed in E006AA cells.
Moreover, the evidence of this novel "loss-of-function" mutation might be extremely useful as a new genetic diagnostic marker for the early identification of the APRT deficiency.
Most are gain-of-function mutations, increasing IKs, IKr, or IK1 and expected to shorten ERP and promote reentry, although an IKur loss-of-function mutation might prolong ERP.
Although the examples given above concern loss-of-function mutations, alternative situations can also fit the definition of synthetic lethality; for example, a gain-of-function mutation might be lethal only in the presence of a simultaneous second-site mutation, or a drug treatment that selectively kills cells carrying a specific genetic alteration.
This mutation might eliminate or alter the function of the prox1 gene [ 35].
