Hong Kong’s first large-scale genome sequencing project has completed its target in advance by having recruited 52,000 patients so far, with a case leading to the revelation of a previously undocumented disease — a strong testament to the genome data base’s contribution to human genomic medicine.

Brian Chung Hon-yin, chief medical and scientific officer of the Hong Kong Genome Institute (HKGI), said in an interview the project had recruited 52,000 patients as of mid-October, completing in advance its initial goal of 40,000 to 50,000 patients by 2025.

Patients of the Hong Kong Genome Project, which started in 2021, are referred by doctors from public hospitals. The number of hospitals joining the project has so far grown from three to 12. The initial three were Hong Kong Children’s Hospital, Prince of Wales Hospital and Queen Mary Hospital all of which have established partnering centers with the HKGI to help recruit eligible patients.

Chung said the project’s goal is to create a genome database for the population in southern China, testing infrastructure and talent pools to advance research in genomic science, and to avail genomic medicine to all for better health and well-being.

In one case, genome sequencing helped identify a genome missense variant on gene PSMF1 in a 16-year-old patient that caused motor delay problems, as well as progressive deterioration in walking and cognition.

The patient underwent whole genome sequencing and RNA sequencing in 2022 and was later diagnosed with PSMF1-associated complex neurodevelopmental disorder a new disease discovered through investigations into the teenager’s case.

During the three-year investigation into the root causes of the patient’s condition, the institute, in collaboration with international medical groups, found 22 patients in 17 families who had similar symptoms without knowing the reason.

“Prior to 2022, there had been no documented case of disease caused by the PSMF1 gene variant globally. This case has provided important reference for patients affected by the same genome variant,” Chung said.

Thanks to the accurate diagnosis, the patient is being treated with new medicine and therapy, he added.

The genome sequencing test, which can take between 45 hours and three years to complete, is a process of locating one specific genome missense variant relating to the patient’s disease out of four million known missense variants identified in the human genome.

Scientifically, only 2 percent of those known variants are said to have a clinical annotation.

According to Chung, the institute will focus on pharmacogenomics at the next stage to ascertain how a person’s genes can affect the response to drugs.

Currently, most medicines are prescribed in one-size-fits-all manner, based on a patient’s weight and age, Chung said. Yet, people with varying genetic makeups respond differently to the same medicines. “We hope to find a safer and more accurate, personalized medication for patients,” he said.

Chung plans to make an announcement about pharmacogenomics at the upcoming International Genomic Medicine Symposium on Nov 17, co-organized by HKGI, Rare Diseases International and the Lancet Commission on Rare Diseases (LCRD) for the first time. The one-day symposium is set to welcome local and international genomics leaders from over 20 countries and regions, including clinicians, scientists and researchers from the Chinese mainland, Europe, North and South America, and Australia.

Zhang Shuyang, president of Peking Union Medical College Hospital in China, and Kym Boycott, professor of pediatrics at the University of Ottawa in Canada and also co-chair of the LCRD, will be among the speakers on genome medicine.

Nearly 300 industry professionals are expected to attend the symposium.

The LCRD, for the first time, will host its annual meeting in Hong Kong on the two days following the symposium — the first time it will be held in Asia.

Chung said the Hong Kong Genome Project aims to attract another 60,000 to 70,000 patients by 2030, a goal likely to be achieved beforehand.

Given the enormous size of the data involved, the institute will spare no effort in safeguarding patients’ privacy and ensuring that the data is soundly saved in the city, Chung said.

Currently, the institute receives possible patient cases every two days. It also provides rapid tests with the aim of producing results in two weeks to help urgent cases. In a recent urgent case, a newborn, who had been on extracorporeal membrane oxygenation in the Neonatal Intensive Care Unit, had the result in 45 hours after a request from doctors. The quick response also helped the doctor to accurately plan therapy treatment and surgery for the newborn.

“For about 77 percent of our patients, genome sequencing has led to optimized medicines or surgical procedures, resulting in improvement,” Chung said.

Derek Lee of the Hong Kong College of Physicians said genome sequencing, which has been widely applied in rare disease diagnosis, has now been used to ascertain common diseases as well.

Citing cardiomyopathy, he said about 1 to 2 percent of the population suffer from cardiomyopathy, with 50 percent of these cases related to genome variants.

One of Lee’s patients — a 27-year-old female — is among the beneficiaries of the sequencing project. She was diagnosed with multifocal ectopic premature Purkinje-related complexes syndrome — a disorder caused by missense genome variant of SCN5A gene.

The insights into her condition have inspired Lee to introduce a fresh treatment plan that involves giving her specialized antiarrhythmic medicine to help her heart regain function and enables her to successfully get pregnant via in vitro fertilization.

Contact the writer at stushadow@chinadailyhk.com