Publication date: Jun 08, 2019
With an initial target of 10,000 volunteers, aged 18 years and above, to date over 2000 participants with no known pre-existing health conditions have consented to undergo a detailed health screen, collection of family health history (FHH) and lifestyle activity information and a genetic screen using whole genome sequencing technology.
As such, the PRISM institute was purpose-built to include a research facility to correlate genomic and clinical data using bioinformatics analytics and a clinical facility comprising of genetic counselling, medical examination and clinical consultation rooms.
Participants are informed that only genes associated with clinical actionability will be reviewed and could indicate: Participants are informed that a genetic counsellor is available during the recruitment appointment to aid in the decision regarding the option to receive genomic findings.
To avoid any confusion, training and handouts were provided to the clinical research coordinators to assist the collection of relevant family history and it is explained to the participants that information from only blood-related family members is relevant.
The additional genes considered for analysis are based on the reported experience of international genomics experts and the local experience of genetic conditions found prevalent in Southeast Asian populations.
Additionally, our SEC local genomic database is analysed to understand carrier prevalence of genetic conditions that are more common in the local population, including diseases such as thalassaemia (1 in 25), citrin deficiency (1 in 41) and Wilson disease (1 in 103). 8,14,15,16,17,18 The ACMG framework was used as a guide for assessing the clinical actionability of genes in our panel. 19 Subsequently, the screening recommendations for each associated genetic condition were then reviewed to ensure that a management plan for ongoing follow-up could be offered in the Singapore context.
Additionally, six genes (KCNE3, CACNA1C, CACNB2, GPD1L, HCN4, SCN3B) were removed from the PRISM gene list because the disease association with Brugada syndrome was classified as -Disputed” in ClinGen. 20 In addition, there is limited evidence for the association of HCN4 with familial thoracic aortic aneurysm and aortic dissection, and no reported evidence for the association of CACNB2 with hypertrophic cardiomyopathy. 21 The PRISM gene list version 2 contains 115 genes associated with Mendelian disorders and 22 pharmacogenomic genes (further details in Supplementary text).
Of these variants, information in accordance with the ACMG variant classification guidelines23 is prepared and presented at a monthly multidisciplinary team (MDT) meeting comprising of clinical genetics, research and bioinformatics experts and critically reviewed.
For these variants, which are classified as variants of unknown significance (VUS), if additional information such as further FHH or a routine clinical laboratory test to ascertain the phenotype, such as a lipid profile, will assist with the interpretation, then these participants are also recontacted.
|disease||MESH||family health history|
|disease||MESH||congenital adrenal hyperplasia|
|disease||DOID||congenital adrenal hyperplasia|
- Genetic Medicine Is Poised to Create New Inequality. Here’s How to Fix It.
- [The roles and regulation mechanism of transcription factor GATA6 in cardiovascular diseases].