Resequencing array for gene variant detection in malignant hyperthermia and butyrylcholinestherase deficiency

Area of Science:

• Pharmacogenetics
• Anesthesiology
• Molecular Diagnostics

Background:

• Malignant hyperthermia (MH) and butyrylcholinesterase (BCHE) deficiency are critical pharmacogenetic disorders in anesthesia.
• Current genetic testing often misses unknown or rare variants in key genes like RyR1, CACNA1S, and BCHE.

Purpose of the Study:

• To develop and validate a novel resequencing DNA array, the perioperative patient safety (POPS) array.
• To enable comprehensive screening of the entire coding sequences of RyR1, CACNA1S, and BCHE genes.

Main Methods:

• Development of the POPS array for high-throughput genotyping.
• Genotyping of 121 MH-susceptible individuals using the POPS array.
• Comparison with capillary sequencing for accuracy and efficiency.

Main Results:

• The POPS array achieved high call rates (up to 100%) and specificity (>99%) for RyR1, CACNA1S, and BCHE genes.
• Successfully detected known pathogenic variants in MH-susceptible individuals.
• Discovered novel variants in previously uncharacterized MH-susceptible subjects.

Conclusions:

• The POPS array is an efficient, high-throughput tool for diagnostic genotyping of genes associated with MH and BCHE deficiency.
• This array facilitates comprehensive screening for both known and rare variants, enhancing perioperative patient safety.
• Enables discovery of new genetic variants contributing to neuromuscular disorders.