A systematic analysis of mitochondrial aminoacyl tRNA synthetase variants in a rare disease cohort.
WHY IT MATTERS
If you or your child has unexplained seizures, developmental delays, or neurological symptoms, this research provides doctors with a new tool to identify whether mitochondrial aminoacyl-tRNA synthetase variants are the cause—potentially leading to a diagnosis after years of testing.
Scientists studied a large group of patients in Europe with rare diseases caused by problems in mitochondrial aminoacyl-tRNA synthetases—proteins that help mitochondria (the energy centers of cells) make other proteins. They found 38 patients with 63 different genetic changes and created a method to match patients' symptoms with similar cases in medical literature, which helps doctors figure out what disease a patient actually has.
A systematic analysis of mitochondrial aminoacyl tRNA synthetase variants in a rare disease cohort. Abstract: Mitochondrial aminoacyl-tRNA synthetases (mt-aaRSs) are a group of proteins encoded by nuclear DNA that play a crucial role in mitochondrial protein synthesis. Mitochondrial diseases caused by mt-aaRS variants are phenotypically heterogenous but often present with significant neurological features such as childhood-onset encephalopathy and seizures. As such, these conditions are a diagnostic challenge. We present an approach that systematically quantifies phenotypic similarity of individuals with an mt-aaRS variant to published cases, to aid variant interpretation, in RD-Connect-a large Europe-wide rare disease cohort. Across 98 individuals with a mt-aaRS gene of interest, we prioritised 38 individuals with 63 variants following bioinformatic and manual analyses. We additionally reviewed E Authors: Ratnaike et al. Journal: European journal of human genetics : EJHG MeSH: Humans, Amino Acyl-tRNA Synthetases, Mitochondrial Diseases, Rare Diseases, Phenotype, Mitochondria, Male, Female, Cohort Studies
ASK YOUR DOCTOR
If you have a family member with unexplained neurological symptoms or seizures without a diagnosis, ask your neurologist or geneticist whether mitochondrial aminoacyl-tRNA synthetase variants have been tested and whether they're aware of this RD-Connect diagnostic approach.