What causes OCLN-related disorder at the molecular level?
The cells lining our blood vessels including the tiny blood vessels in the brain are held together by structures called tight junctions, which act like seals between neighboring cells. The OCLNgene makes a protein called occludin, one of the main building blocks of these seals. In the brain, tight junctions form part of the blood-brain barrier, a protective barrier that controls what can pass from the bloodstream into the brain.
When both copies of the OCLNgene are mutated, occludin does not work properly, and the seals between blood vessel cells in the brain become "leaky." This is thought to lead to the calcium deposits and unusual brain folding pattern seen in this condition.
What type of genetic change causes this condition?
Unlike some other genetic conditions where almost everyone shares the same mutation, OCLN-related disorder is caused by many different types of changes, and different families often carry their own unique mutation. That said, one specific deletion has been found repeatedly in Egyptian families, suggesting it may be a more common cause of this condition specifically within the Egyptian population.
Testing for OCLNmutations can be technically tricky, because there is a very similar "decoy" sequence elsewhere in our DNA (a pseudogene) that can confuse standard genetic tests. Specialized laboratory techniques are often needed for an accurate result.
How is the diagnosis made?
The diagnosis is suspected based on the characteristic combination of symptoms and brain scan findings, and confirmed through genetic testing of the OCLNgene. Usually requiring specialized testing methods because of the pseudogene mentioned above. Once a mutation is confirmed in an affected child, both parents should be tested to confirm they are carriers.
OCLN