Molecular genetic testing approaches used in achromatopsia can include targeted analysis for the common CNGB3 variant c.1148delC (p.Thr383IlefsTer13), use of a multigenerational panel, or comprehensive genomic testing. ACHM2
While some mutations in CNGA3 result in truncated and, presumably, non-functional channels this is largely not the case. While few mutations have received in-depth study, at least one mutation does result in functional channels. Curiously, this mutation, T369S, produces profound alterations when expressed without CNGB3. One such alteration is decreased affinity for Cyclic guanosine monophosphate. Others include the introduction of a sub-conductance, altered single-channel gating kinetics, and increased calcium permeability.When mutant T369S channels coassemble with CNGB3, however, the only remaining aberration is increased calcium permeability. While it is not immediately clear how this increase in Ca2+ leads to achromatopsia, one hypothesis is that this increased current decreases the signal-to-noise ratio. Other characterized mutations, such as Y181C and the other S1 region mutations, result in decreased current density due to an inability of the channel to traffic to the surface. Such loss of function will undoubtedly negate the cone cells ability to respond to visual input and produce achromatopsia. At least one other missense mutation outside of the S1 region, T224R, also leads to loss of function. ACHM3
While very few mutations in CNGB3 have been characterized, the vast majority of them result in truncated channels that are presumably non-functional. This will largely result in haploinsufficiency, though in some cases the truncated proteins may be able to coassemble with wild-type channels in a dominant negative fashion.
Congenital oculomotor palsy
The origins of the vast majority of congenital oculomotor palsies are idiopathic. There is some evidence of a familial tendency to the condition, particularly to a partial palsy involving the superior division of the nerve with an autosomal recessive inheritance. The condition can also result from aplasia or hypoplasia of one or more of the muscles supplied by the oculomotor nerve. It can also occur as a consequence of severe birth trauma. Acquired oculomotor palsy
Vascular disorders such as diabetes, heart disease, atherosclerosis and aneurysm, particularly of the posterior communicating artery
Space occupying lesions or tumours, both malignant and non-malignant
Inflammation and infection
Trauma
Demyelinating disease (multiple sclerosis)
Autoimmune disorders such as myasthenia gravis
Post-operatively as a complication of neurosurgery
Cavernous sinus thrombosis

Mechanism
As the pair of oculomotor nerves arises from different subnuclei in the midbrain, courses through different structures in the brain and branches into superior and inferior divisions after exiting the cavernous sinuses, any lesions along its path will produce different pathological features of the third nerve palsy. The parasympathetic aspect of the nerve (which constricts pupils and thicken the lens) is located on the nerve surface, supplied by pial blood vessels. The nerves core contains the main trunk of the oculomotor nerve, supplied by vasa vasorum. Thus pathologies affecting the nerves core without affecting the superficial part of the nerve (thus sparing the pupillary reflex) are known as "medical" oculomotor nerve palsy.