Clinical trial NCT06450964: Establishment of Reproductive Cohort and Prediction Model of Genetic Counseling for Mitochondrial Genetic Diseases
Official title: Establishment of Reproductive Cohort and Prediction Model of Genetic Counseling for Mitochondrial Genetic Diseases
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Mitochondrial Diseases
Keywords: mitochondrial diseases
mitochondrial DNA mutation
reproductive cohort
genetic counseling
Lead sponsor: Anhui Medical University
Sponsor class: OTHER
First posted: 2024-06-10
Enrollment: 600
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: mtDNA mutation carriers from The First Affiliated Hospital of Anhui Medical University

Brief 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.

Detailed 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.

Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of mitochondrial DNA diseases

Exclusion Criteria:

* none

Primary outcomes:
measure: Symptoms of mitochondrial disease
timeFrame: 3 years
Secondary outcomes:
measure: level of mitochondrial DNA mutation
timeFrame: 3 years
measure: Tissue-specific distribution of mitochondrial DNA mutation levels
timeFrame: When they enrolled
Other outcomes:
Locations:
city: Hefei
country: China
facility: First Affiliated Hospital of Anhui Medical University
state: Anhui
Study officials:
affiliation: The First Affiliated Hospital of Anhui Medical University
name: Dongmei Ji, Dr.
role: STUDY_CHAIR
References: