APPLICATION OF NON-INVASIVE PRENATAL SCREENING FOR MULTIPLE MITOCHONDRIAL DYSFUNCTION SYNDROME TYPE 3

Multiple mitochondrial dysfunction syndrome type 3 (MMDS3) is a rare autosomal recessive neurogenetic disorder caused by pathogenic variants in the IBA57 gene. Disorder is clinically represented by loss of motor skills, intellectual impairment, and a decrease in the quality of life. Therefore, early and accurate prenatal diagnostics are essential for risk assessment. We report a family case in which prenatal screening detected the IBA57 mutation. A non-consanguineous family with a previously diagnosed child with MMDS3. Molecular diagnostics included non-invasive prenatal testing using cell-free fetal DNA (cffDNA) to assess for known familial IBA57 variants. Targeted Sanger sequencing was performed for the IBA57 variants c.286T>C and c.667C>G. Parental testing demonstrated obligate heterozygosity: the mother carried c.286T>C and the father c.667C>G. The c.286T>C variant was not detected, while a heterozygous c.667C>G variant was identified. The newborn was therefore classified as an unaffected heterozygous carrier of IBA57. As a result of prenatal testing, the child should be observed further by a neurologist. This case demonstrates the importance of integrating prenatal diagnostic strategies, including cffDNA analysis, with confirmatory postnatal testing in pregnancies at high genetic risk when invasive prenatal diagnosis is not possible. Such an approach allows accurate exclusion of severe mitochondrial disease, supports informed clinical decision-making, and provides essential guidance for genetic counseling in future pregnancies. This research has been funded by the Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan (No. BR27199879).