#ScienceSaturday posts share exciting scientific developments and educational resources with the KAND community. Each week, Dr. Dylan Verden of KIF1A.ORG summarizes newly published KIF1A-related research and highlights progress in rare disease research and therapeutic development.

KIF1A-Related Research

Cerebral Visual Impairment: genetic diagnoses and phenotypic associations

Knowing which symptoms are associated with a disease is crucial for managing, treating, or curing patients with that disease. But the opposite relationship is just as important: knowing which diseases are associated with a symptom means earlier diagnosis, and an earlier search for other potential symptoms.

Studies that investigate the genetics of patients with specific symptoms are a powerful tool; they can encourage the inclusion of genes on symptom-based genetic panels, and help clinicians identify potential disease causes. In this week’s pre-print*, researchers investigated the genetics of patients with cerebral visual impairment.

Cerebral/Cortical Visual Impairment

Vision is much more than our eyes; it is a complex set of circuits that has interactions throughout our brain. When people have visual deficits that can’t be explained by issues in the eye, it is called cerebral (brain-related) visual impairment. The 2021 Natural History Study found that about 20% of KAND patients experience cerebral visual impairment, but the incidence is likely higher. Why would KIF1A dysfunction alter visual processing in the brain?

The neurons that make up your optic nerve travel to the thalamus, an integrative area in the middle of your brain that coordinates your visual field with other senses like hearing and balance. Neurons in the thalamus send projections to the visual cortex at the back of your head before connecting to additional visual processing areas.

Our visual system relies on timely coordination between many distant brain regions (Laurent Perrinet).

These long-range projections may be vulnerable to the loss of long-range motor proteins like KIF1A, which could compromise visual circuits and cause subtle phenotypes, including:

  • Abnormal response to light, or changes in brightness.
  • Lack of social gaze
  • Avoidance of novel stimuli
  • Ability to navigate or react visually despite other visual deficits

The Study

The researchers probed two large patient databases for patients with cerebral visual impairment who had undergone genetic testing. KIF1A was identified in cases from both databases, supporting the relationship between KIF1A mutations and cerebral visual impairment. But notably, KIF1A was just 1 of 173 identified genes, highlighting the utility of genetic testing for patients with cerebral visual impairment.

The researchers also investigated other symptoms that tend to coincide with cerebral visual impairment, noting a higher incidence of seizures and dystonia. Understanding how these symptoms cluster may inform clinicians as they perform additional testing or recruit additional experts in the treatment of patients with cerebral visual impairment.

*What’s a pre-print? Check out this #ScienceSaturday post to learn more

Rare Roundup

n-Lorem hosts Nano-rare Patient Colloquium

This week n-Lorem hosted its nano-rare patient colloquium to discuss lessons learned in its goal to provide n-of-1 treatments to rare disease patients. The day featured the journeys of pioneer patients like our very own Susannah Rosen, examples of n-Lorem’s pipeline from a patient perspective, as well as productive conversations about the integration of clinical, industry, and patient stakeholders to accelerate the search for, and application of, ASO-based treatments. You can find the entire colloquium recording below:

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