Spanish Registry of RYR1 and CACNA1S Polymorphisms

NCT03964870 | Unknown

• 1 other identifier: RYCA
• Study Type: observational
• Target: 5,000
• Locations: 1 country
• Sites: 1

Brief Summary

Study design: The Spanish registry of RYR1 and CACNA1S polymorphisms (RYCA) is an anonymous descriptive observational multicentre study that aims to identify and catalogue the variants or polymorphisms in the RYR1 and CACNA1S genes in the Spanish population. Secondarily, its correlation with the binding mutations described in both genes at European level by the EMHG will be evaluated to assess the incidence of malignant hyperthermia in Spain. The RYCA registry complies with the highest standards of European and international homologation, both with regard to computer security and the protection of personal data (Data Protection Law 15/1999). Hypothesis: Performing a Spanish registry of RYR1 and CACNA1S polymorphisms will contribute to describe the variants present in our environment and determine their relationship with MH susceptibility. Objectives:

• Describe the national polymorphisms of the RYR1 and CACNA1S genes
• To evaluate the incidence of genetic MH susceptibility according to the recommendations of the EMHG. The presence of polymorphisms in a population that has not been studied before may have a difficult correlation with the mutations described in the EMHG webpage. Eligibility Criteria: The sample contained in the registry will originate from the genetic data of patients unrelated to HM who have been sequenced the RYR1 and CACNA1S gene by another pathology. The data related to the genetic analysis will be provided without identifying data of the patient or the clinical history. There will be no possibility of identification of the patient by the team responsible for the RYCA registry, so the request for informed consent is not viable. There will be no selection of participants or patient follow-up. Methodology: A preliminary pilot study will be conducted in an unselected anonymous cohort of the sequenced exome database of the RYR1 and CACNA1S gene at the La Fe Health Research Institute (IISlaFe). The population contained in this database is random and unrelated to HM and the patients are anonymous, so we do not have access to personal data or medical history. If the analysis is feasible, a request for collaboration will be transferred to the Genetics Services / Research Units with experience in the exome sequencing of the RYR1 and CACNA1S genes. Anonymous readings will be requested to carry out the registration and description of the variants existing in the Spanish population and their relationship with the variants described by the EMHG. Variables: The registry will include the chromosomal coordinates, number of total patients included, number of patients whose variant is in heterozygosis, number of patients whose variant is in homozygosis and allelic frequency. Thus, for each of the genes of interest, and making use of their respective chromosomal coordinates, information regarding the variants that these might include will be extracted. Sample size. Sample size calculation is not considered since it is a descriptive record.

Conditions

Malignant Hyperthermia; Polymorphisms in Genes RYR1 and CACNAS1S

Keywords

Malignant Hyperthermia

Outcome Measures

Primary Outcomes (2)

• Describe the national polymorphisms of the RYR1 and CACNA1S genes

  The peripheral blood must be extracted by venous puncture. For this, it is necessary to carry out the extraction of the blood by qualified health personnel respecting the corresponding hygienic-sanitary norms. The blood must be in a tube with EDTA anticoagulant (preferably). The method of extraction of peripheral blood DNA: is carried out mainly by automatic procedure using the QIASYMPHONY SP DNA extractor-purifying equipment and the QYASIM DNA MIDI KIT Kit (Qiagen), Cat. No: 931255, following the manufacturer's protocols. The DNA extraction stage is collected in the GESTLAB system as SAMPLE PROCESSING (it comprises extraction and quantification via Nanodrop, as indicated below).

  Day 1

• To evaluate the incidence of genetic MH susceptibility according to the recommendations of the EMHG.

  The peripheral blood must be extracted by venous puncture. For this, it is necessary to carry out the extraction of the blood by qualified health personnel respecting the corresponding hygienic-sanitary norms. The blood must be in a tube with EDTA anticoagulant (preferably). The method of extraction of peripheral blood DNA: is carried out mainly by automatic procedure using the QIASYMPHONY SP DNA extractor-purifying equipment and the QYASIM DNA MIDI KIT Kit (Qiagen), Cat. No: 931255, following the manufacturer's protocols. The DNA extraction stage is collected in the GESTLAB system as SAMPLE PROCESSING (it comprises extraction and quantification via Nanodrop, as indicated below).

  Day 1

Interventions

Diagnostic of polymorphisms in malignant hyperthermia DIAGNOSTIC_TEST

Identify and catalogue the variants or polymorphisms in the RYR1 and CACNA1S genes in the Spanish population.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Inclusion Criteria: Patents with malignant hyperthermia which genes RYR1 and CACNA1S have been sequenced for another pathology

The sample contained in the registry will originate from the genetic data of patients unrelated to malignant hyperthermia who have been sequenced the RYR1 and CACNA1S gene by another pathology. The data related to the genetic analysis will be provided without identifying data of the patient or the clinical history. There will be no possibility of identification of the patient by the team responsible for the RYCA registry, so the request for informed consent is not viable. There will be no selection of participants or patient follow-up.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Hospital Universitario La Fe: lead

Study Sites (1)

IIS la Fe

Valencia, 46026, Spain

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples to identify genes RYR1 and CACNAS1S

MeSH Terms

Conditions

Malignant Hyperthermia

Condition Hierarchy (Ancestors)

Intraoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Postoperative Complications; Hyperthermia; Body Temperature Changes; Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator of Anesthesiology

Study Record Dates

• First Submitted: May 22, 2019
• First Posted: May 28, 2019
• Study Start: December 5, 2018
• Primary Completion: November 5, 2020
• Study Completion: December 5, 2020
• Last Updated: May 29, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)