Multigenerational Brazilian family with malignant hyperthermia and a novel mutation in the RYR1 gene
Braz. j. med. biol. res
; 42(12): 1218-1224, Dec. 2009. tab, ilus
Article
in En
| LILACS
| ID: lil-532288
Responsible library:
BR1.1
ABSTRACT
Malignant hyperthermia (MH) is a pharmacogenetic disease triggered in susceptible individuals by the administration of volatile halogenated anesthetics and/or succinylcholine, leading to the development of a hypermetabolic crisis, which is caused by abnormal release of Ca2+ from the sarcoplasmic reticulum, through the Ca2+ release channel ryanodine receptor 1 (RyR1). Mutations in the RYR1 gene are associated with MH in the majority of susceptible families. Genetic screening of a 5-generation Brazilian family with a history of MH-related deaths and a previous MH diagnosis by the caffeine halothane contracture test (CHCT) in some individuals was performed using restriction and sequencing analysis. A novel missense mutation, Gly4935Ser, was found in an important functional and conserved locus of this gene, the transmembrane region of RyR1. In this family, 2 MH-susceptible individuals previously diagnosed with CHCT carry this novel mutation and another 24 not previously diagnosed members also carry it. However, this same mutation was not found in another MH-susceptible individual whose CHCT was positive to the test with caffeine but not to the test with halothane. None of the 5 MH normal individuals of the family, previously diagnosed by CHCT, carry this mutation, nor do 100 controls from control Brazilian and USA populations. The Gly4932Ser variant is a candidate mutation for MH, based on its co-segregation with disease phenotype, absence among controls and its location within the protein.
Key words
Full text:
1
Index:
LILACS
Main subject:
Pedigree
/
Ryanodine Receptor Calcium Release Channel
/
Mutation, Missense
/
Malignant Hyperthermia
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Female
/
Humans
/
Male
Country/Region as subject:
America do sul
/
Brasil
Language:
En
Journal:
Braz. j. med. biol. res
Journal subject:
BIOLOGIA
/
MEDICINA
Year:
2009
Type:
Article