Four diseases, One Gene: CACNA1A

Written by Dr. Judit Pérez Edited by Dr. David Bushart

A new case report describes how a new mutation in the CACNA1A gene causes ataxia with seizures.

Genes and their diseases

Hereditary ataxias are caused by mutations in different genes that affect how different parts of the brain and spinal cord work. Usually, the affected genes predict how one would expect the patient’s clinical signs and symptoms to look. The reverse can also be true. For example, a set of clinical signs and symptoms may raise suspicion of a known genetic disease, which allows doctors to perform focused genetic testing to confirm the diagnosis. These correlations are helpful for doctors and patients in understanding the diagnostic process and disease outlook.

New mutation, new disease

A study by Stendel and colleagues was inspired by a patient who developed ataxia in mid-adulthood that slowly worsened over the next decades of his life. The progression resembled that of spinocerebellar ataxias with repeat expansions in their genes as the culprits. However, when doctors performed the usual genetic testing for ataxia genes, they did not find a match. Nevertheless, suspicion for an ataxia gene playing a role remained high. The patient had experienced seizures as a child (called “absence seizures”), which didn’t entirely fit the picture of known SCAs. Where to go from here? The scientists next broadened their search to include 118 genes that are known to cause ataxia or other diseases that include ataxia symptoms.  To their surprise, they found a previously unidentified mutation in a well-known ataxia gene called CACNA1A.

Human brain digital illustration. Electrical activity, flashes and lightning on a blue background.
CACNA1A is a gene that instructs brain cells to make a protein called Cav2.1, which helps neurons communicate. But now mutations in the CACNA1A gene are now connected to four different diseases. Photo used under license by Yurchanka Siarhei/Shutterstock.com.
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