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

Conditions
Mitochondrial Diseases
Registration Number
NCT06450964
Lead Sponsor
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.

Recruitment & Eligibility

Status
ENROLLING_BY_INVITATION
Sex
All
Target Recruitment
600
Inclusion Criteria
  • Clinical diagnosis of mitochondrial DNA diseases
Exclusion Criteria
  • none

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Symptoms of mitochondrial disease3 years

The enrolled patients were followed up once a year. Symptoms that the patient has due to mitochondrial DNA mutations are recorded.

Secondary Outcome Measures
NameTimeMethod
Tissue-specific distribution of mitochondrial DNA mutation levelsWhen they enrolled

The levels of mitochondrial DNA mutations in blood, urine, oral epithelial cells, nails, etc. were measured when the patients were enrolled.

level of mitochondrial DNA mutation3 years

The enrolled patients were followed up once a year. Levels of mitochondrial DNA mutation are measured by next generation sequencing and ddPCR.

Trial Locations

Locations (1)

First Affiliated Hospital of Anhui Medical University

🇨🇳

Hefei, Anhui, China

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