Abstract
Objectives: To identify genetic factors contributing to patient with inherited heart diseases, to create a
genotype-phenotype association database, to perform genetic screening in family members, and determine
the yield and cost-effectiveness of genetic testing.
Methodology: This study aimed to identify the genetic causes of heart diseases through Whole Genome
Sequencing (WGS). Clinical data and genetic findings were collected into a database (using the Redcap
program) and analysis were perform at a population level. Patients with negative results or Variants of
Unknown Significance (VUS) may undergoes further examination if there is a potential in providing additional
diagnostic value (new genes or new variants) either through Triple Exome Study, Segregation Analysis, or
Functional Analysis. For patients with positive results, the findings were used in the screening of their family
members. The outcomes were examined for cost-effectiveness using an economic simulation model
(Markov Model).
Results: Genetic testing results of 13 6 patients currently in the database demonstrate 5 2 . 21% detection
rate for pathogenic or likely pathogenic variants. Differences in detection rate was observed across different
heart diseases, such as long QT syndrome (60%) and CPVT (100%) patients. Some variants were identified
in more than one patient, which may indicate the presence of founder effect within the population.
Variation in phenotypes was also observed in patients carrying the same mutation. For example, the KCNQ1
c.1032G>C variant in Long QT syndrome patients or the SCN5A p. R965C variant in Brugada syndrome
patients. Since these variants affect a high portion of cases (due to the founder effect), further studies to
understand the factors that affect the phenotypes would benefit a significant number of Thai patients.
The cost-effectiveness analysis of genetic testing for patients with Long QT syndrome found
it to be economically efficient in public health terms, with a cost efficiency of 128,180 THB/QALY.
The findings further highlight the importance of genetic testing in patients and relatives either
to diagnose the disease, interpret variant of uncertain significance, or for effective screening of relatives
high-risk for developing the disorder. Lastly, this study demonstrated the cost-effectiveness of genetics
testing in proband and relative in certain disease, considering quality of life, life expectancy, and treatment
costs.
Conclusion: Genetic testing proves to be valuable diagnostic tool for heart disease patients and their family
members, potentially reducing the risk of heart-related complications and improving treatment efficiency.
Disease-causing variants identified in Thai heart disease patients are unique from previously reported in
other countries. A database of Thai patients serves as a crucial foundation in studying genotype-phenotype
relationships. Additionally, it enables investigation of variants effect at a population level.
