Gene Mutation Spectrum of Malignant Hyperthermia in China

Title:

Recruitment Status:

Recruiting

Status Last Updated:

July 22, 2020

Clinical Phenotype(s):

Malignant Hyperthermia susceptibility - MHS1 (RYR1)

Gene(s):

RYR1

Study Purpose:

In this study, case information and specimens of patients with malignant hyperthermia(MH) will be collected from all over China, and gene fragment analysis, sanger sequencing method and/or high-throughput whole-genome sequencing will be performed. The MH bioinformatics database will be established to find the pathogenic gene and mutation site of MH in Chinese. Based on the bioinformatics database, the genetic law of MH family will be studied. According to the results of the study, the guideline for the diagnosis and treatment of MH that is in line with Chinese population biology characteristics will be formulated.

Intervention/Treatment:

Diagnostic Test: gene sequencing

Phase:

Not Applicable

Study Description:

When MH cases or suspected cases occur in China, anesthesiologists can seek help through malignant hyperthermia emergency rescue WeChat group in which experts from all over the country will give therapy instructions. Afterwards, the responsible anesthesiologist will complete the case report form (CRF) and collect family history of MH. The quality of CRF is reviewed by the investigator and all the queries are solved within 1~2 weeks.

Upon obtaining the informed consent, all biological specimens of MH confirmed or suspected patients and their blood relations will be collected in the local hospitals and transported to West China Hospital, Sichuan University in dry ice packaging. All specimens will be checked by the trained investigator, registered and labeled in a standardized manner, and then stored in the biological sample bank of West China Hospital, Sichuan University.

Firstly, investigators will use the method of gene fragment analysis to detect the samples at the diagnostic mutation sites included in the current European malignant hyperthermia group. Secondly, investigators will use sanger sequencing method to verify the mutation variants. If the screening results are negative, then high-throughput whole-genome sequencing will be performed.

The MH bioinformatics database will be established to find the pathogenic gene and mutation site of MH in Chinese. Based on the bioinformatics database, the genetic law of MH family will be studied. According to the results of the study, the guideline for the diagnosis and treatment of MH that is in line with Chinese population biology characteristics will be formulated.

Study Type:

Observational

Official Title:

Study on Gene Mutation Spectrum of Malignant Hyperthermia in China Based on the Establishment of Bioinformatics Database

Study Start Date:

January 15, 2019

Study Completion Date:

January 2024

Primary Objective(s):

Pathogenic gene and mutation site of MH in Chinese [ Time Frame: Within data collection period (5 years total) ]
Samples from patients with MH and their blood relations in China will be detected by gene fragment analysis and then verified by Sanger sequencing method and/or detected by high-throughput whole-genome sequencing to find the pathogenic gene and mutation site of MH in Chinese.

Secondary Objective(s):

Clinical profiles and outcomes of patients with MH in China [ Time Frame: Within data collection period (5 years total) ]
This study will summarize the Clinical profiles of patients with MH in China by collecting and analyzing case information of patients with MH from all over China.
The genetic law of MH family [ Time Frame: Within data collection period (5 years total) ]
Collecting samples from the MH patients and their blood relations and undertaking gene fragment analysis, Sanger sequencing method and/or high-throughput whole-genome sequencing, family genitive tree for MH will be then drawn.

Eligibility:

Ages Eligible for Study: Child, Adult, Older Adult

Sexes Eligible for Study: All

Accepts Healthy Volunteers: Yes

Sampling Method:Non-Probability Sample

Inclusion Criteria:

Chinese whose malignant hyperthermia susceptibility had been confirmed after a positive clinical manifestation of malignant hyperthermia which defined as their scores of clinical grading scale for malignant hyperthermia are more than 35 and their blood relations.

Sign informed consent

Exclusion Criteria:

Patients who have no adverse anaesthetic event, such as those patients referred with a history of exertional heat illness, exertional or recurrent rhabdomyolysis, or a congenital myopathy.

Study Site(s)/Location(s):

China, Sichuan

West China Hospital, Sichuan University

Chengdu, Sichuan, China, 610041

Sponsors & Collaborators:

West China Hospital

Principal Investigator(s):

Principal Investigator: Bin Liu, MD West China Hospital

Principal Investigator: Yunxia Zuo, MD West China Hospital

For more information, please contact the Study Coordinator:

Contact:

Email:

Phone:

ClinicalTrials.gov ID:

NCT04474860