A KCNQ4 c.546C>G Genetic Variant Associated with Late Onset Non-Syndromic Hearing Loss in a Taiwanese Population

Clinical presentation is heterogeneous for autosomal dominant nonsyndromic hearing loss (ADNSHL). Variants of KCNQ4 gene is a common genetic factor of ADNSHL. Few studies have investigated the association between hearing impairment and the variant c.546C>G of KCNQ4. Here, we investigated the phenotype and clinical manifestations of the KCNQ4 variant. Study subjects were selected from the participants of the Taiwan Precision Medicine Initiative. In total, we enrolled 12 individuals with KCNQ4 c.546C>G carriers and 107 non-carriers, and performed pure tone audiometry (PTA) test and phenome-wide association (PheWAS) analysis for the patients. We found that c.546C>G variant was related to an increased risk of hearing loss. All patients with c.546C>G variant were aged >65 years and had sensorineural and high frequency hearing loss. Of these patients, a third (66.7%) showed moderate and progressive hearing loss, 41.7% complained of tinnitus and 16.7% complained of vertigo. Additionally, we found a significant association between KCNQ4 c.546C>G variant, aortic aneurysm, fracture of lower limb and polyneuropathy in diabetes. KCNQ4 c.546C>G is likely a potentially pathogenic variant of ADNSHL in the elderly population. Genetic counseling, annual audiogram and early assistive listening device intervention are highly recommended to prevent profound hearing impairment in this patient group.

Precision Medicine: Making It Happen for Malaysia

Precision medicine is transforming healthcare worldwide and aims to improve the effectiveness of management of many diseases including cancers, other non-communicable diseases (NCDs) and also rare diseases. Precision medicine takes into account the individual patient’s genetic, environment and lifestyle data. Developed nations are already embarking on precision medicine initiatives including the 100,000 Genomes England and the Precision Medicine Initiative in the United States (US). The Academy of Sciences Malaysia, the Ministry of Health and the Ministry of Higher Education are working together to put forward a precision medicine initiative for Malaysia. The key drivers that must be put in place include a strong policy agenda, a national large scale genome sequencing project and with it a national genome database, the implementation of the electronic medical record (EMR) system, a payment and reimbursement system to cover for the genetic testing and the targeted treatment, and putting in place an ecosystem that will support precision medicine. Relevant guidelines and Acts will also need to be developed especially with regard to privacy and confidentiality. The future of precision medicine is now and this will certainly bring better outcome and value to the patients.

Progress in Clinical Neurosciences, Cognitive Neurosciences, Clinical Psychology, Neurotechnology and Brain Mapping in Malaysia

Last year, there was an increase in the amount of manpower in Malaysia, especially in terms of the numbers of neurosurgeons, cognitive neuroscientists and clinical psychologists. One way to increase the number of cognitive neurotechnologists in the country in 2021 is to allow neuroscientists to register as neurotechnologists with the Malaysian Board of Technologists (MBOT). The Malaysian Brain Mapping project has risen from its humble beginnings as an initiative of the Universiti Sains Malaysia Brain Mapping Group in 2017. There is currently a proposal for its entry into the national arena via the Precision Medicine Initiative with the Academy Science Malaysia, the Ministry of Science, Technology and Innovation, Ministry of Higher Education and Ministry of Health. The current Malaysian Government’s Science, Technology, Innovation and Economy (STIE) plan was launched in 2020, leading to the establishment of neurotechnology as one of 10 STIE drivers.

A new precision medicine initiative at the dawn of exascale computing

Which signaling pathway and protein to select to mitigate the patient’s expected drug resistance? The number of possibilities facing the physician is massive, and the drug combination should fit the patient status. Here, we briefly review current approaches and data and map an innovative patient-specific strategy to forecast drug resistance targets that centers on parallel (or redundant) proliferation pathways in specialized cells. It considers the availability of each protein in each pathway in the specific cell, its activating mutations, and the chromatin accessibility of its encoding gene. The construction of the resulting Proliferation Pathway Network Atlas will harness the emerging exascale computing and advanced artificial intelligence (AI) methods for therapeutic development. Merging the resulting set of targets, pathways, and proteins, with current strategies will augment the choice for the attending physicians to thwart resistance.

Evaluation of clinical impact of pharmacogenomics knowledge involved in CPIC guidelines on Chinese pediatric patients

Aim: To evaluate the clinical benefits of implementing pharmacogenomics testing for Chinese pediatric patients. Materials & methods : Based on the drug–gene interactions involved in the Clinical Pharmacogenetics Implementation Consortium guidelines, whole-genome sequencing data from the Chinese Academy of Sciences Precision Medicine Initiative project and the medication data of pediatric patients from a children's hospital, the prevalence of the Chinese population with actionable pharmacogenomic variants was calculated, the prescribing pattern for pediatric patients was analyzed. Results: 37.0% of the drugs involved in the Clinical Pharmacogenetics Implementation Consortium guidelines were used by Chinese pediatric patients, 8.91% inpatients and 0.89% outpatients received at least one pharmacogenomics medication, 1.24% (4803) inpatients and 0.16% (2940) outpatients were estimated to be at high risk of pharmacogenomic-related adverse therapeutic outcomes. Conclusion: Implementing pharmacogenomics testing can improve therapeutic outcomes for many Chinese pediatric patients.