The unhappy fate of two families helped an international team of scientists discover a genetic syndrome that causes deadly lung infections in children around one year of age. Experts from Masaryk University who participated in the research examined the properties of a protein that helps repair damaged chromosomes which can otherwise cause this very rare disease in small children.
“Dutch physicians came across one of the cases of this syndrome when they found out that two siblings died several years one after another, both when they were about a year old. They started looking for a possible genetic cause and found a mutation that could be linked to the deaths. The suspicion was confirmed when another family with a similar medical history and the same gene mutation was found,” says biochemist Jan Paleček about how the research into the syndrome started. The gene mutation causes the production of the wrong protein. The produced protein is part of a complex labelled as SMC5/6. Together with two other complexes, it is responsible for storing and preserving the genetic information in the cell in the form of chromosomes.
As Paleček explains, “Condensin, cohesin, and SMC5/6 are three protein complexes that help ensure that DNA totalling several metres in length can fit into a cell only several micrometres in size. If these complexes malfunction, chromosomes can get damaged.”
In the case of this particular genetic syndrome, the SMC5/6 complexes do not hold together, the chromosomes get broken, and the body’s immune system is weakened, which means that a lung infection can be lethal. “We helped our colleagues explain how damage to the protein impacts its properties,” says Paleček, adding that the research into the syndrome took several years.
The mutation is relatively common in the Netherlands, with three people in a thousand affected. Its occurrence in the rest of Europe is lower. However, as Paleček stresses, “The mutation may not manifest itself at all. It has to be present in both parents and both must pass the mutation down to their child.” Both affected Dutch families have several healthy children.
No cure as yet
There is no prevention against – or cure for – this rare disease as yet. A family in the US carry a mutation of a different part of this gene, which has an even worse impact on the functioning of the protein complex.
The authors of the study hope that by publishing their discovery, they can help clinicians identify other cases of this syndrome. “If there are Czech doctors who have encountered similar cases of child deaths, or who will see such cases in the future, we can help them perform a genetic analysis of the child’s family members and retrospectively establish the cause of death,” says Paleček. “We will try to learn more about this syndrome and maybe also discover other syndromes caused by damaged chromosomes in human cells.”