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No association between the neuroleptic malignant syndrome and mutations in the RYR1 gene associated malignant
R Miyatake1, K Iwahashi, M Matsushita
1Department of Neuropsychiatry, Kagawa Medical School, Japan.
Abstract:
The neuroleptic malignant syndrome (NMS) is a drug-induced disease caused by neuroleptics, but the pathogenesis of NMS is unknown. Since NMS is similar to malignant hyperthermia (MH) in clinical features and treatment, 6 mutations in the skeletal muscle ryanodine receptor (RYR1) gene, which were associated with MH, were investigated in unrelated NMS patients by single-strand conformation polymorphism analysis (SSCP). As a result, MH-susceptible RYR1 mutations were not detected in our NMS patients. A single base substitution, C7278T, was detected in one patient whose serum CPK level was repetitively elevated, but his other major symptoms did not fulfil the clinical criteria for NMS. Our results do not support the association between the neuroleptic malignant syndrome and mutations in the RYR1 gene associated with malignant hyperthermia.
Insights
This study investigated if mutations in the skeletal muscle ryanodine receptor (RYR1) gene, linked to malignant hyperthermia, cause neuroleptic malignant syndrome. Researchers found no association between RYR1 mutations and neuroleptic malignant syndrome in NMS patients.
Area of Science:
- Pharmacology
- Genetics
- Neurology
Background:
- Neuroleptic malignant syndrome (NMS) is a severe drug-induced condition with unknown pathogenesis.
- NMS shares clinical and treatment similarities with malignant hyperthermia (MH).
- The skeletal muscle ryanodine receptor (RYR1) gene is implicated in MH.
Purpose of the Study:
- To investigate the potential association between NMS and RYR1 gene mutations known to cause MH.
- To determine if specific RYR1 mutations are present in patients diagnosed with NMS.
Main Methods:
- Single-strand conformation polymorphism (SSCP) analysis was used.
- Six known MH-susceptible RYR1 mutations were screened.
- Unrelated NMS patients were analyzed for these mutations.
Main Results:
- No MH-susceptible RYR1 mutations were detected in the NMS patient cohort.
- A single base substitution (C7278T) was found in one patient with elevated CPK, but this patient did not meet full NMS criteria.
- The identified RYR1 variant did not correlate with the clinical presentation of NMS.
Conclusions:
- The findings do not support a link between NMS and the investigated RYR1 gene mutations associated with MH.
- RYR1 mutations common in MH are unlikely to be a primary cause of NMS.
- Further research is needed to elucidate the pathogenesis of NMS.