Examination of an Estonian patient helped discover a new form of muscular dystrophy

In about a quarter of patients with hereditary diseases, the cause of the disease remains unclear even after extensive genetic testing. One reason is that we still do not know enough about the function of many genes. Of the 30,000 known genes, just a little more than 4,000 have been found to be associated with hereditary diseases.

At the Department of Clinical Genetics of the University of Tartu Institute of Clinical Medicine, under the leadership of Professor Katrin Õunap, patients with hereditary diseases of unclear cause have been studied in various research projects since 2016. In collaboration with the Broad Institute of MIT and Harvard, these patients have undergone extensive genome-wide sequencing analyses at the level of the exome (the sequence of all genes), genome (whole DNA sequence), and transcriptome (RNA transcribed from the genome).

Professor Katrin Õunap described that in a girl with progressive muscle weakness, they found two changes in the JAG2 gene that had not been associated with any hereditary disease before. “In cooperation with an international team of researchers, we found 22 other patients with similar problems and changes in the JAG2 gene from all over the world,” said Õunap.

The study showed that the misfunction of the JAG2 gene interferes with the development of muscle cells and their ability to recover, thereby causing progressive muscle damage.

Estonian researchers conducted a transcriptome (RNA) analysis of the patient’s muscle tissue, which provided important information on pathological changes in gene expression in muscle cells. “Also, for the first time in Estonia, our patient underwent a special muscular magnetic resonance imaging scan, which revealed a pattern of muscle involvement characteristic of pathogenic variants in JAG2 in lower limb muscles,” explained Õunap.

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The article was published in the American Journal of Human Genetics in cooperation with researchers from Estonia, Belgium, the United States, the United Kingdom, France, Germany, Poland, Iran, Egypt and Japan.