Next-Generation Sequencing to Determine the Genetic Etiology of Fetal Skeletal Abnormalities Detected by Prenatal Ultrasound

Background: Fetal skeletal dysplasia is a group of disorders that cause abnormal bone growth and development in the fetus, resulting in severe complications and economic burdens on healthcare systems. This study aims to enhance the diagnosis and management of fetal skeletal dysplasia by examining its phenotypes, genetic causes, and the connection between genetic mutations and observed traits. Methods: We performed a retrospective analysis of 28 prenatal cases diagnosed with fetal skeletal dysplasia using advanced genetic testing methods such as whole exome sequencing, chromosomal analysis, and single nucleotide polymorphism (SNP) array analysis. Results: Our findings revealed diverse phenotypic presentations, with 24 cases exhibiting limb shortening, and distinct genetic inheritance patterns: parental dominant (PAD), de novo mutations (DNMs), autosomal recessive (AR), and cases without pathogenic mutations (UN). Prenatal ultrasound was crucial for early detection and influenced management strategies. Additionally, SNP array analysis combined with short tandem repeats (STR) confirmed the biological relationship between the fetus and the mother, ensuring the integrity of the data. Exome sequencing identified candidate mutation sites, and whole genome sequencing provided insights into structural variations, facilitating personalized management approaches. Conclusions: This study highlights the importance of early diagnosis and genetic counseling for at-risk families and emphasizes the need for further research to confirm genetic findings and investigate potential future therapies based on the identified mutations. Our research contributes valuable insights into the genetic and clinical characteristics of fetal skeletal dysplasia, paving the way for improved diagnostic accuracy and patient outcomes in affected families.