09 July 2020
Developmental disorder linked to autophagy
Published online 8 January 2013
Vici syndrome is a rare congenital disorder characterized by cataracts, cardiomyopathy, callosal agenesis (in which connections between the brain's hemispheres fail to develop), albinism and immunodeficiency. It is more common among consanguineous families, suggesting that it is a heritable condition.
An international team of researchers, including two scientists from Saudi Arabia and one from the United Arab Emirates, sequenced the exomes — portions of a person's genome expressed — of four infants of European, Arab, Turkish, Japanese and British-Asian origin, publishing their findings in Nature Genetics.
They found that all four children shared a mutation to one gene: EPG5. Further analysis in a total of 18 individuals from 15 families revealed mutated forms of EPG5 in all but two people. The gene is expressed in the central nervous system, thymus, lungs, kidneys, and skeletal and cardiac muscles, and encodes a key autophagy regulator. Autophagy is a tightly controlled cellular process that removes damaged or unwanted cellular components, crucial for the health of all cell types, including those involved in muscles, the immune system and brain development.
Abnormalities in autophagy have already been implicated in neurodegenerative conditions, but defects causing developmental disorders such as Vici syndrome are less established. The researchers suggest that defunct autophagy could play a key role in causing a range of disorders.
"Although the condition is very rare, it is likely that insights provided by research into Vici syndrome will also be transferable to the diagnosis and therapy of neurodegenerative and neurodevelopmental disorders, and a wider range of primary muscle conditions," says Heinz Jungbluth, one of the study's lead authors.
- Cullup, T. et al. Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy. Nature Genetics 45, 83-87 (2013)