In our discussion of cytoskeletal proteins, I said that we would not expect to find mutations in proteins like actin/tubulin, since they are so important in so many cellular functions.  However, this statement overlooks an important fact.  In vertebrates there are  mutliple isoforms of actin and tubulin.
While there are currently no known mutations in tubulin associated with human disease,
two mutations in cardiac muscle a-actin have been identified.
These mutations are associated with idiopathic hypertrophic cardiomyopathy.
 

Figure from Mooseker & Cheney. 1995. Unconventional Myosins.  Ann. Rev. Cell Deve. Biol. 11:633-675.

Myosins are well known as motor proteins, associated with actin and actin filaments.  There are many distinct types of myosins, however, in addition to the well known proteins associated with the contractile apparatus of muscle.  Mutations in cardiac muscle myosins (and their associated proteins) have been linked to hypertrophic cardiomyopathy. The different myosins differ in a number of ways.  The most obvious is the types of interactions that they can make with themselves and other cellular proteins, which typically involves their "tail" domain.  In muscle myosins, the tails assembly in both parallel and anti-parallel manners to form "thick filaments".  The tail domains of other myosins mediated different types of interactions.

Motor proteins, like kinesins (which run on microtubules), which transport vesicles          have fairly long processivity (otherwise the vesicle would float away from the MT).      some myosins, like myosin VA also seem to have long processivity. Figure from review article by Margaret Titus

Myosins also differ from one another in terms of "Processivity"     essentially, how long the myosin will walk along the actin filament before it falls off.

Mutations in myosin V are associated with mutations in the dilute locus in mice and are associated with Griscelli Disease in humans-associated with  defects in pigmentation and  lethal defects in immune system cell proliferation (from OMIM - "Most 'dilute' alleles also produce a neurologic defect characterized by convulsions and opisthotonus, apparent at 8 to 10 days of age, and continuing until the death of the animal at 2 to 3 weeks of age")

Treatment for Griscelli disease involves bone marrow transplantation, presumably to regenerate normal immune system function. Initial mouse mutation due to insertion of murine leukemia virus (dV allele) made isolation of gene easier (how?)   Linked to defects in the positioning of melasomes (pigment particles) and their transmittion to other cells.   In the homozygous state - neonatal lethal.

Mutations in unconventional myosins found to underlie two mouse mutations: the Snell's Waltzer deafness mouse is in the gene for myosin VI, whereas the mutation found in the shaker-1 mouse is mutated in myosin VII While no mutation in myosin VI has been linked to deafness in humans.  Mutations is the human homolog of the myosin VII gene causes Ussher syndrome type I, which is associated with deafness and progressive loss of sight.   In the case of myosin VII, which localized to the lower regions of the actin bundle in the stereocilia, its absence presumably leads to an altered mechanics.   In the mouse, myosin VII is found in the retinal epithelial, and the absence of myosin VII is associated with a defect in pigment distribution, similar to that seen in myosin V mutant animals.

In the stereocilia, myosin Ib is localized to the tip of the hair follicle; it appears to be involved in anchored actin filaments at that site and controlling the response of the stereocilia to mechanical deformation (adaption).  Movement of the tip in response to sound gnerates changes in intracellular Ca2+, that  travel into the cell body and lead to signals.  Mutations in myosin Ib have not yet been identified in humans.