While investigating a rare developmental disease, a team of scientists ended up discovering a spectrum of diseases that are all linked to one gene.
One recently published in the journal Genetics in Medicine, about a rare disease in a single patientsolved medical mysteries affecting at least 30 people.
These patients presented a wide variety of symptoms, from developmental delays to bone malformations and even premature death.
However, the study authors found that they all suffered from diseases caused by a mutation in same gene, called FLVCR1 — which controls the transport of two essential nutrients, hill ea ethanolaminein cells.
Both choline and ethanolamine have a fundamental role in metabolism — the chemical reactions that provide energy to the body, explained to the study’s lead author, Daniel Calameprofessor of pediatric neurology and developmental neurosciences at Baylor College of Medicine in Texas.
“Taking this into consideration and the fact that the FLVCR1 is expressed throughout the bodyit makes sense that one could have a wide spectrum of problemsdepending on the severity of the deficit in choline/ethanolamine transport”, stated Calame.
The first patient in the study was treated at the Calame clinic at Texas Children’s Hospital. Presented severe developmental delays neurological, a history of seizures and, surprisingly, I didn’t have the capacity to feelr.
Seizures and neurodevelopmental delays are a common combination of symptoms, but The child’s lack of pain sensation was unusualexplains Calame. The boy and his parents had already undergone genetic testing, but no one had been able to identify the root cause of his disorder.
So, Calame and his team delved deeper into this data, studying the entire constellation of genes in the boy’s genome that code for proteins. They noticed that there was a very rare mutation in both copies of the FLVCR1 gene.
This fact caught Calame’s attentionbecause the gene had previously been associated with very different diseases which involved muscle coordination and retinal degradation, respectively.
These were very different symptoms from those seen in his patient, Calame acknowledged. But there was a common point: in some cases, patients with these other diseases also had reduced sensitivity to pain.
“There was a bit of overlap,” notes Calame.
The FLVCR1 gene had also been studied in mice. When the gene was eliminated from rodent embryos, his absence caused a stillbirth. The stillborn rats had bone and brain malformations, as well as severe anemia.
To find out what was going on, Calame and his team turned to their own DNA database of more than 12,000 individuals with genetic diseases and contacted other research labs around the world with similar data.
They identified 30 patients from 23 different families with FLVCR1 mutations. There were 22 mutations in total, 20 of which had never been recorded before.
Some of the 30 individuals were stillborn due to serious developmental problems in the womb. Others survived but suffered developmental delays, bone malformations or microcephaly, a condition in which the skull is smaller than it should be.
In laboratory experiments, Long Nam Nguyenassociate professor at the National University of Singapore and co-author of the study, investigated the function of FLVCR1.
This investigation revealed the role of the gene in the movement of choline and ethanolamine in cells, helping to explain how a single genetic change can affect so many systems in the body.
Calame and his team are now collecting blood samples from patients with FLVCR1 mutations to see if they can find a way to treat these rare diseases. In some cases, it is possible that the cell supplementation more choline and ethanolamine might help, Calame said.
Alternatively, researchers may have to use another medicine to prevent the accumulation of toxins that can occur when fundamental cellular processes do not function correctly.
The research could have implications for other conditions involving choline, an essential nutrient that people can get from leafy greens, beans and many animal products.
Choline deficiency has been associated with nerve damage age-related and neurodegenerative diseases such as Alzheimer’s disease, says Calame. “He has many implications beyond this disease very rare.”
