A newly identified KIF5A variant disrupted exon 27 splicing in laboratory-grown motor neurons
Original source
Consequences of the Novel ALS-Associated KIF5A Variant c.2993-6C > A for Exon 27 Splicing and Axonal Transport of SFPQ. (opens in a new tab)Compass summarised this from the study's abstract.
Study details
- Studied in
- Human
Population inferred from the title and abstract by Compass.
Related topics
Researchers identified the KIF5A variant c.2993-6C > A in a family affected by amyotrophic lateral sclerosis (ALS). In induced pluripotent stem cell-derived neurons, the variant caused skipping of exon 27 and disrupted transport of a KIF5A cargo. Under stress conditions, motor neurons carrying the variant developed TDP-43 proteinopathy.
Why this matters
The findings link this specific KIF5A variant to cellular changes associated with ALS and suggest a possible disease mechanism. The work was done in laboratory-grown cells, so it does not yet change treatment or show that the variant causes ALS in people.
Limitations and context
This was a laboratory study involving cells derived from siblings in one ALS-affected family. It shows that the variant affects splicing and transport in cultured neurons, but does not establish its frequency, clinical effects, or causation in the wider ALS population. The authors describe it as a possible risk factor and propose a mechanism that requires further confirmation in people and other models.