Molecular Genetic Analysis and Prenatal Diagnosis of a Family With MECP2 Duplication Syndrome

OBJECTIVE: This study aimed to conduct a molecular genetic analysis and prenatal diagnosis for a family with MECP2 duplication syndrome (MDS), with the goal of improving diagnostic accuracy and enabling informed reproductive decisions to reduce the incidence of this condition. METHODS: The study involved a proband (a 15-week-old fetus), his symptomatic older brother, and their parents. Genomic DNA from chorionic villus and peripheral blood samples was analyzed using high-throughput sequencing to detect chromosomal copy number variations (CNVs). To confirm the findings, multiplex ligation-dependent probe amplification (MLPA) was specifically employed. RESULTS: High-throughput sequencing identified a 0.35 Mb duplication at Xq28 in the fetus and his mother, and a 0.4 Mb duplication in the brother. The duplicated region contained the critical MECP2 gene. MLPA analysis confirmed the MECP2 gene duplication in the fetus, leading to a definitive diagnosis of MDS. The mother was identified as an asymptomatic carrier. CONCLUSION: Both the proband and his brother were diagnosed with MDS, having inherited the duplication from their asymptomatic mother. The combined use of high-throughput sequencing and MLPA proved to be an effective strategy for accurate pedigree analysis and prenatal diagnosis of MDS, providing a crucial basis for genetic counseling.