DNA Test Assesses Risk of Malignant Hyperthermia

The new technique, called high resolution melting (HRM) curve analysis, provides a sensitive and specific tool for the identification of genetic variants responsible for MH and a much simpler alternative to currently available tests.

At Skåne University Hospital Lund (Malmö, Sweden) scientists developed an approach to assessing the risk of MH by using a sample of DNA extracted from a blood sample. Fragments of DNA from the ryanodine receptor 1 (RYR1) gene are identified and gradually heated to assess the temperature at which the strands of DNA begin to unwind. Fragments with unusual, or aberrant melting profiles can undergo full gene sequencing to pinpoint specific variants potentially causing MH.

The scientists evaluated the HRM curve analysis approach in 16 MH susceptible patients. All had either experienced a life-threatening episode of MH themselves, had a close relative who had died of MH, or had undergone the muscle biopsy test for suspected abnormalities. A total of approximately 2,500 DNA fragments underwent HRM curve analysis. The test showed significantly aberrant melting profiles in 21% of the DNA fragments tested. Subsequent gene sequencing studies identified 131 variants known to cause MH, along with 17 known or suspected mutations. Overall, 13 of the 16 MH-susceptible patients had genetic abnormalities known or suspected of causing MH, which is a rate of 81%. The use of HRM curve analysis to look for MH-related mutations of the RYR1 gene would greatly reduce the need for in-depth gene sequencing studies, without sacrificing test sensitivity.

Malignant hyperthermia is a rare condition in which genetically susceptible people develop rapid increases in body temperature and muscle rigidity in response to certain anesthetics and other drugs. Once the condition is recognized, it can generally be avoided by substituting other anesthetics. However, susceptible patients generally go unrecognized until they or a family member experience an episode of MH. The study was published in the November 2011 edition of the journal Anesthesia & Analgesia.

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