A new ALS gene discovery – KIF5A - funded by The ALS Association, with money raised through the ALS Ice Bucket Challenge, will help drive new discoveries and fuel the ALS treatment pipeline.

Below are some common questions and answers – written by Dr. John Landers, author of the recently published KIF5A Neuron paper – along with places to read more information.

Are KIF5A mutations associated with both familial (inherited) and sporadic (non-inherited) ALS?

We have identified two types of KIF5A mutations that contribute to familial and sporadic ALS. These mutations are different from mutations that cause SPG10, a rare form of hereditary spastic paraplegia (HSP), a slowly progressive neurodegenerative disease.

Familial ALS refers to ALS in which more than one family member is affected by the disease. About 10 percent of all people with ALS have familial ALS. The other 90 percent of ALS is called sporadic, meaning it has not occurred in another member of the family.

In familial ALS cases, we have identified mutations that cause the KIF5A protein to be shortened, meaning that the full KIF5A protein is not made. In sporadic ALS, we observe a change in a single amino acid in the KIF5A protein.

Amino acids are the building blocks of protein. When there is an amino acid change or a change to the length of a protein, the protein composition changes, which may impact protein function.

This contrasts with mutations of a different single amino acid in the KIF5A protein that cause HSP/SPG10.

How is the KIF5A gene inherited?

Mutations that appear to contribute to SPG10/HSP and familial ALS appear to be inherited in an autosomal dominant fashion.

Autosomal dominant inheritance is when a person carries one mutated gene copy and one normal gene copy and disease occurs. The disease-causing mutation can be inherited from either parent. The chances of inheriting the mutation is 50 percent for each child of either sex, and a child who inherits the mutation will usually develop the disease.

For more information on ALS genetics, click here.

Is genetic testing available for the KIF5A mutations?

Clinical testing is currently being conducted for KIF5A for the HSP/SPG10. This could be applicable to KIF5A for familial ALS. Information on companies performing clinical testing can be found at the following web sites. (You’ll need to copy/paste them into your web browser.)

https://www.ncbi.nlm.nih.gov/gtr/conditions/C1858712/
https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=C1858712&filter=testtype:clinical
https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=3798[geneid]

For more information on genetic testing and genetic counseling, click here.

To read another article about this gene discovery, click here.

To view the open access paper on the Neuron journal website, click here.

Paper citation
Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
Nicolas, A., et al. 21 March 2018, Neuron 97, 1268–1283