Research article summary (published 30 Dec 1994):

C1840-T mutation in the human skeletal muscle ryanodine receptor gene: frequency in northern German families susceptible to malignant hyperthermia and the relationship to in vitro contracture response.

Full Abstract

In swine, a point mutation in the ryanodine receptor gene can account for all cases of malignant hyperthermia (MH). The frequency of a corresponding mutation in humans (C1840-T) and its relationship to the in vitro contracture profile is unknown. We screened 192 patients from 28 unrelated northern German families for the C1840-T mutation in the human ryanodine receptor gene and tested for MH susceptibility using the in vitro contracture test (IVCT) according to the European MH Protocol. In our patients 106 revealed MH susceptible (MHS), 56 MH nonsusceptible and 30 MH equivocal status following IVCT. In each family one or two individuals had developed clinical signs of MH or a MH crisis. All of these patients were classified MHS. The C1840-T mutation was found in 2 of 28 families (7.1%). All eight individuals of the two families characterized by this mutation revealed MHS status following IVCT. The thresholds for halothane- and caffeine-induced contractures as well as the contracture profiles following cumulative (0.4-10.0 mumol/l every 3 min) and bolus (10 mumol/l) administration of ryanodine were found to be similar in MHS patients with and without the C1840-T mutation. In conclusion, the C1840-T mutation in the human ryanodine receptor gene is a rare abnormality in MHS families. Similar contracture profiles in the presence and absence of this mutation might imply no major functional role with respect to the contracture response. At present, molecular genetic analysis cannot replace IVCT to discover MH susceptibility in humans.

Author information

Author/s: Steinfath, M (M); Singh, S (S); Scholz, J (J); Becker, K (K); Lenzen, C (C); Wappler, F (F); Köchling, A (A); Roewer, N (N); Schulte am Esch, J (J);

Affiliation: Abteilung für Anästhesiologie, Universität Hamburg, Universitäts-Krankenhaus Eppendorf.

Journal and publication information

Publication Type: In Vitro; Journal Article

Journal: Journal of molecular medicine (Berlin, Germany) (J Mol Med), published in GERMANY. (Language: eng)

Reference: 1995-Jan; vol 73 (issue 1) : pp 35-40

Dates: Created 1995/09/12; Completed 1995/09/12; Revised 2006/11/15;

PMID: 7633940, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Adolescent Adult Aged Base Sequence Caffeine - pharmacology Calcium Channels - genetics Child Child, Preschool Chromosomes, Human, Pair 19 Disease Susceptibility Female Halothane - pharmacology

Humans Male Malignant Hyperthermia - genetics Middle Aged Molecular Sequence Data Muscle Contraction - drug effects Muscle Proteins - genetics Muscle, Skeletal - chemistry; drug effects Point Mutation - genetics Polymorphism, Genetic - genetics Ryanodine - pharmacology Ryanodine Receptor Calcium Release Channel

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Calcium Channels (0) ; Muscle Proteins (0) ; Ryanodine Receptor Calcium Release Channel (0) ; Halothane (151-67-7) ; Ryanodine (15662-33-6) ; Caffeine (58-08-2)

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