Mitochondrial Diseases
Conditions
Keywords
mitochondrial diseases, mitochondrial DNA mutation, reproductive cohort, genetic counseling
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.
Interventions
OTHERBiological 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.
Sponsors
Anhui Medical University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of mitochondrial DNA diseases
Exclusion criteria
* none
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Symptoms of mitochondrial disease | 3 years | The enrolled patients were followed up once a year. Symptoms that the patient has due to mitochondrial DNA mutations are recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| level of mitochondrial DNA mutation | 3 years | The enrolled patients were followed up once a year. Levels of mitochondrial DNA mutation are measured by next generation sequencing and ddPCR. |
| Tissue-specific distribution of mitochondrial DNA mutation levels | When they enrolled | The levels of mitochondrial DNA mutations in blood, urine, oral epithelial cells, nails, etc. were measured when the patients were enrolled. |
Countries
China
Outcome results
None listed