National Bio Big Data Initiative addresses rare disease patients wandering for diagnosis

On Tuesday, Seoul National University Hospital announced that a collaborative research team — led by Professors Chae Jong-hee, Moon Jang-sup, and Lee Seung-bok of the Department of Clinical Genomics and Professor Choi Jung-min of the Department of Biomedical Sciences at Korea University – produced the results by analyzing large-scale genomic information from patients who visited Seoul National University Hospital between 2019 and 2023 and the Korea Biobank Cohort.

NIID disease is a neurodegenerative disorder characterized by the accumulation of abnormal proteins (inclusion bodies) in the nuclei of nerve cells. The disease is caused by a “single nucleotide repeat mutation” in the NOTCH2NLC gene, an abnormal repetition of the GGC sequence. It usually develops in adulthood and is accompanied by various neurological symptoms, including leukoencephalopathy, progressive cognitive dysfunction, and ataxia.

However, conventional next-generation sequencing using short-reads, which analyze the genome in short chunks, has faced limitations in identifying short-chain repeat patterns, making it difficult to make an accurate genetic diagnosis even in cases of suspected NIID.

The research team built a state-of-the-art sequencing technique that introduces a long-read method that analyzes long-unit genomes to identify short-chain repeat variants. Using this method, the researchers analyzed the whole genome data of 90 patients with unexplained leukoencephalopathy who visited Seoul National University Hospital and had imaging evidence of NIID.

The results showed that 16 patients (17.8 percent) had a single-chain repeat mutation, meaning that one to two out of every 10 patients with unexplained leukoencephalopathy in Korea have the rare NIID. This supports previous findings that the disease is frequent in East Asians, the team explained.

Furthermore, the team analyzed genomic information from 3,887 Korean rare disease patients and their families at the Korean Biobank Cohort to determine the distribution of GGC sequence repeats in the NOTCH2NLC gene, and found that the disease can be presumed when the sequence is repeated “65 or more times.”

As a result of applying these criteria, six undiagnosed neurodegeneration patients listed in the Korean Biobank were newly diagnosed with NIID.

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Sources : KBR (https://www.koreabiomed.com)

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