An international team of researchers has successfully diagnosed 30 individuals with a previously undiagnosed condition through the identification of a rare genetic mutation. The study, led by Baylor College of Medicine and National University of Singapore, was published in Genetics in Medicine.
Dr. Daniel Calame, an instructor at Baylor, described the case that initiated the research: “The story of our findings began with one patient I saw in the clinic presenting an uncommon combination of problems.” This patient exhibited severe developmental conditions, epilepsy, and insensitivity to pain. Despite extensive testing by specialists, the condition remained undiagnosed until further analysis pointed to a gene called FLVCR1.
Research into FLVCR1 revealed its role in producing red blood cells and transporting crucial cellular components like choline and ethanolamine. These elements are vital for cell membrane integrity and division. Animal studies showed that removing this gene resulted in embryonic lethality due to bone malformations and defective red blood cell production.
Although previous studies linked FLVCR1 mutations to other conditions such as Diamond-Blackfan anemia (DBA) and ataxia, Dr. Calame noted discrepancies: “We were intrigued... Could it be that those different mutations of FLVCR1 caused not one set but a spectrum of characteristics we observed in all the patients combined?”
To address this question, researchers examined large datasets to find individuals with undiagnosed neurodevelopmental disorders linked to FLVCR1 variants. They identified 30 patients from 23 families with unique genetic variants.
The study found 22 variants, most previously unreported. Affected individuals exhibited symptoms ranging from severe developmental disorders to premature death. Laboratory experiments showed these variants reduced choline and ethanolamine transport significantly.
“Our findings also support further studying the potential therapeutic value of choline or ethanolamine supplementation in FLVCR1-related diseases,” said Calame. He emphasized the importance of broad diagnostic approaches for rare conditions: “Such false assumptions illustrate the importance of incorporating model organism data into personalized genome analysis.”
For more details on authorship and funding, refer to the publication.
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