Where Do the Gene Changes Happen?
The DNM1Lgene has different parts (called domains) that help the protein it makes do its job. Harmful changes (called pathogenic variants) have been found in all of these parts:
• GTPase domain
• Middle domain (MD)
• GED domain
What Symptoms Are Linked to Each Part?
All patients with DNM1L-related changes show neurological symptoms (problems with the brain and nervous system).
If the change is in the middle or GED domain, people often have:
• Brain dysfunction (encephalopathy)
• Developmental regression (losing skills they had already learned)
If the change is in the GTPase domain, people often have:
• Nerve damage in the limbs (peripheral neuropathy)
• Balance problems (ataxia)
• Muscle stiffness or spasms (spasticity)
• Involuntary muscle movements (dystonia)
• Changes in the middle domain are also more likely to cause:
• Seizures
• Severe, hard-to-stop seizures (status epilepticus)
• Brain shrinkage (cerebral atrophy)
How Are These Changes Inherited?
Most of the harmful changes are missense variants (where just one building block of the gene is changed). These usually happen spontaneously (de novo) — not inherited from parents — and cause the dominant form of the condition (only one copy of the gene needs to be changed). Rarer cases are inherited in a recessive way (both copies of the gene must be changed). These are often truncating variants, which stop the protein from being made properly.
DNM1L