The FLVCR1 gene is involved in transporting choline and ethanolamine, which are essential for maintaining the integrity of cell membranes and cell division. These compounds are important for the production of phosphatidylcholine and phosphatidylethanolamine, which are important for normal development. According to Daniel Kalam, the study’s lead author and an instructor of pediatric neurology at Baylor College, a patient with a rare FLVCR1 mutation experienced severe developmental disabilities, epilepsy, and a complete lack of sensitivity to pain, which became the starting point for studying the gene.
In an analysis of 23 families, the researchers found 22 unique FLVCR1 mutations, 20 of which were previously unknown. The conditions identified included severe developmental delays, microcephaly, brain abnormalities, epilepsy, and anemia. These findings were consistent with studies in animal models where knocking out the FLVCR1 gene caused severe developmental abnormalities and early death.
To understand the impact of these mutations, scientists conducted laboratory experiments that showed that mutations reduce the transport of choline and ethanolamine by 50% compared to the norm. A decrease in the supply of these substances to the central and peripheral nervous systems leads to neurodegenerative diseases and disruption of normal development. According to the researchers, the severity of the disease depends on the degree of activity of the gene's transport function.
Scientists suggest that adding choline or ethanolamine to the diet may help treat diseases associated with the FLVCR1 mutation. Further studies will show how effective this approach is. Kalam noted that the results obtained will help not only diagnose rare diseases, but also improve approaches to their treatment.
The work highlights the importance of using animal models to analyze genetic mutations and the need to consider the broad spectrum of symptoms associated with each gene. FLVCR1 mutations were previously considered unimportant because of the inconsistency of patterns across patients, but pooling them together reveals the overall picture, Kalam noted.
The findings were the key to a diagnosis that patients had been waiting for years. “Finding an answer for 30 people who had remained undiagnosed for a long time is a truly inspiring result,” Kalam added.