Establishment of Reproductive Cohort and Prediction Model of Genetic Counseling for Mitochondrial Genetic Diseases

Mitochondrial Diseases Clinical Trial

Official title:

Establishment of Reproductive Cohort and Prediction Model of Genetic Counseling for Mitochondrial Genetic Diseases

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06450964
• Other study ID #: PJ2024-02-22
• Status: Not yet recruiting
• Start date: September 1, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: June 2024
• Source: Anhui Medical University
• Contact: Dongmei Ji, Dr.
• Phone: +86-551-6590-8445
• Email: jidongmei[@]ahmu.edu.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this observational study is to provide a reference for clinicians to conduct genetic counseling and carry out preimplantation genetic testing of mitochondrial patients. The main questions it aims to answer are:

• The relationship between mitochondrial mutation load and clinical symptom

• The symptomatic threshold of common mitochondrial DNA mutations

• The distribution of mitochondrial mutation load in offspring and genetic rule of mitochondrial DNA mutation

• The minimum number of eggs taken by preimplantation genetic testing in mitochondrial mutation carriers Biological samples such as blood, urine, oral epithelial cells, nails, some granulosa cells, trophoderm cells, embryo culture fluid, embryo biopsy fluid, and embryo trophoblast cells of the participants will be collected and the mutation loads of them will be measured. The clinical symptoms and mutation load of the participants will be followed up once a year.

Description:

A total of 600 carriers of disease-causing mitochondrial DNA mutations will be selected as the research objects. The basic information, reproductive history, clinical and genetic diagnosis, and clinical symptoms of the carriers will be investigated by questionnaire. Biological samples such as blood, urine, oral epithelial cells, nails, some granulosa cells, trophoderm cells, embryo culture fluid, embryo biopsy fluid, and embryo trophoblast cells of the participants will be collected and the mutation loads of them will be measured. Placenta and umbilical cord blood samples of some fetuses will be collected after delivery, and the mitochondrial DNA mutation heterogeneity level will be determined. Multiple Logistic regression, Sewell-Wright equation, Kimura equation, binomial distribution model, and machine learning model will be used to establish a prediction model of the incidence probability of mitochondrial diseases and predict the onset threshold of common mitochondrial DNA mutations after standardizing. The distribution model of mitochondrial mutation load in offspring will be established to predict the maternal genetic risk of mitochondrial DNA mutation. A prediction model for egg retrieval will be established to estimate the minimum number of eggs taken by preimplantation genetic testing in mitochondrial mutation carriers. Finally, an online prediction platform for mitochondrial genetic disease genetic counseling will be established to provide standardized standards for mitochondrial disease genetic counseling and PGT.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 600
• Est. completion date: December 31, 2027
• Est. primary completion date: September 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Clinical diagnosis of mitochondrial DNA diseases

Exclusion Criteria:

• none

Related Conditions & MeSH terms

• Genetic Diseases, Inborn
• Mitochondrial Diseases

Intervention

Other:
• Biological samples such as blood, urine, oral epithelial cells and nails of carriers were collected, and the mitochondrial DNA mutation heterogeneity level was determined.
Biological samples such as blood, urine, oral epithelial cells and nails of carriers were collected, and some granulosa cells, trophoderm cells, embryo culture fluid, embryo biopsy fluid, and embryo trophoblast cells were collected. Placenta and umbilical cord blood samples of some fetuses were collected after delivery, and the mitochondrial DNA mutation heterogeneity level was determined.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Anhui Medical University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Symptoms of mitochondrial disease	The enrolled patients were followed up once a year. Symptoms that the patient has due to mitochondrial DNA mutations are recorded.	3 years
Secondary	level of mitochondrial DNA mutation	The enrolled patients were followed up once a year. Levels of mitochondrial DNA mutation are measured by next generation sequencing and ddPCR.	3 years
Secondary	Tissue-specific distribution of mitochondrial DNA mutation levels	The levels of mitochondrial DNA mutations in blood, urine, oral epithelial cells, nails, etc. were measured when the patients were enrolled.	When they enrolled