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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Mitochondrial Diseases
• Intervention / Treatment: 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.

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.

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230022
      • First Affiliated Hospital of Anhui Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

mtDNA mutation carriers from The First Affiliated Hospital of Anhui Medical University

Description

Inclusion Criteria:

• Clinical diagnosis of mitochondrial DNA diseases

Exclusion Criteria:

• none

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Anhui Medical University
• Investigators: Study Chair: Dongmei Ji, Dr., The First Affiliated Hospital of Anhui Medical University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: June 3, 2024
• First Submitted That Met QC Criteria: June 7, 2024
• First Posted (Actual): June 10, 2024

Study Record Updates

• Last Update Posted (Actual): October 28, 2024
• Last Update Submitted That Met QC Criteria: October 25, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: mitochondrial DNA mutation; genetic counseling; mitochondrial diseases; reproductive cohort
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Mitochondrial Diseases
• Other Study ID Numbers: PJ2024-02-22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No