Korean researchers find gene responsible for neurodevelopmental disorders

A Korean research team has identified a gene mutation that causes neurodevelopmental disorders, including low intelligence and developmental delay.

Professor Chae Jong-hee of the Department of Clinical Genomics at Seoul National University Hospital said Friday that a joint research team identified a variant of the HDAC3 gene associated with neurodevelopmental disorders. HDAC3 is a gene that makes proteins called histone deacetylases that regulate gene expression. So far, the genes responsible for 6,000 to 7,000 rare genetic diseases have been identified, but the causes of many genetic diseases are still unknown.

Professor Chae worked with Professor Yoon Ji-hoon of the Department of Diagnostic Laboratory Medicine at Gangnam Severance Hospital, Professor Lee Chul-hwan, and researcher Lim Sung-kyun of the Department of Pharmacology at Seoul National University College of Medicine.

The researchers reanalyzed whole-exome sequencing (WES) data from 2,510 patients who visited the Center for Rare Diseases at Seoul National University Children’s Hospital over the past decade and found two de novo mutations in the HDAC3 gene in two patients. It was the first study to show that HDAC3 gene variants might be associated with neurodevelopmental disorders.

In addition to the two Korean patients, the team found four more with collaborators in the U.K. and the U.S. Ultimately, they identified six de novo mutations in the HDAC3 gene in six patients.

The team conducted in vitro experiments, cellular experiments, and proteomic analyses to determine the effects of the mutations on HDAC3 function. The results showed that the mutations resulted in reduced histone deacetylase activity (66 percent), impaired protein complex formation (100 percent), and impaired nuclear translocation (75 percent), leading to various neurodevelopmental disorders.

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

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