Clinical trial NCT04474860: Gene Mutation Spectrum of Malignant Hyperthermia in China
Official title: Study on Gene Mutation Spectrum of Malignant Hyperthermia in China Based on the Establishment of Bioinformatics Database
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Malignant Hyperthermia
Keywords: Malignant Hyperthermia
Gene mutation spectrum
Bioinformatics database
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2020-07-17
Enrollment: 200
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Clinically diagnosed MH patients in China and their blood relations

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pathogenic gene and mutation site of MH in Chinese
timeFrame: Within data collection period (5 years total)
Secondary outcomes:
measure: Clinical profiles and outcomes of patients with MH in China
timeFrame: Within data collection period (5 years total)
measure: The genetic law of MH family
timeFrame: Within data collection period (5 years total)
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
Study officials:
affiliation: West China Hospital
name: Bin Liu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: West China Hospital
name: Yunxia Zuo, MD
role: PRINCIPAL_INVESTIGATOR
References: