Central European Journal of Experimental Biology
Abstract
Author(s): Swyeta Jain Gupta*
Background: Malignant Hyperthermia (MH) is a pharmacogenetic syndrome of skeletal muscle. MH occurs due to
abnormal calcium release in the sarcoplasmic reticulum in the skeletal muscles. MH Susceptible (MHS) individuals
are patients suffering from MH when they exposed to anaesthetics. MH is diagnosed in the laboratory by the in vitro
contracture test (IVCT), which is invasive and time consuming procedure. MH causative mutations in the ryanodine
RyR1 channel (RYR1) and Dihydropyridine receptor channel (DHPR) were detected in 70% of the MHS cases.
However, about 30% of UK MHS individuals have no causative mutations in RYR1 and DHPR (CACNA1S) genes.
Objective: The aim of the present study is to investigate the relationships between MH susceptibility and genes
encoding skeletal muscle Ca2+ channels and their accessory proteins. FKBP1A was selected as a candidate gene for
DNA sequencing and mutations detection in individuals with no RYR1 or CACNA1S mutations.
Materials and methods: Genomic DNA was extracted from blood samples obtained from 50 UK MHS patients who
were negative for all causative mutations. DNA sequencing for the entire coding DNA sequence of FKBP1A was
performed successfully.
Results: DNA sequence analysis of FKBP1A gene revealed no novel mutations or any genetic variants that were
identified in 50 MHS individuals.
Conclusion: To our knowledge, the present study is the first DNA sequencing study of FKBP1A gene in MHS
individuals with no RYR1 or CACNA1S mutations. Our results showed no mutations were detected in FKBP1A gene;
therefore, FKBP1A is unlikely to be associated with MH susceptibility.
