J Matern Fetal Neonatal Med. 2025 Dec;38(1):2538208. doi: 10.1080/14767058.2025.2538208. Epub 2025 Jul 28.
ABSTRACT
BACKGROUND: Congenital anomalies are a heterogeneous disorder that occur during fetal development or infancy. Whole exome sequencing (WES) is a promising diagnostic tool for prenatal diagnosis. This study aimed to evaluate the efficiency of WES in identifying the genetic cause of fetal anomalies among Jordanian families.
METHODS: A total of 46 fetuses prenatally diagnosed with various congenital anomalies were included in this study. These cases were categorized into seven groups based on presented phenotypes. DNA was extracted from either chorionic villus samples or amniotic fluid and subjected to singleton WES to identify causative genetic variants. Clinical features and pregnancy outcomes were also collected and reviewed. Variant validation and segregation analysis were performed using ARMS-PCR or Sanger sequencing.
RESULTS: Pathogenic or likely pathogenic variants were identified in 26/46 fetuses (56.5%) and variants of uncertain significance (VUS) were detected in 9/46 fetuses (19.6%). In total, 34 variants in 29 genes were identified including 13 pathogenic, 11 likely pathogenic, and 10 VUS. Twenty-three out of 34 variants have never been published. The identified variants were missense (n = 12, 35%), frameshift (n = 10, 29%), nonsense (n = 7, 21%), splice site (n = 3, 9%), and in-frame deletion (n = 2, 6%). Consanguinity was reported in 42 families (91.3%).
CONCLUSIONS: This study underscores the value of WES in prenatal diagnosis and further expands the mutation spectrum associated with fetal anomalies. It also suggests that WES has strong potential to be used as a routine diagnostic tool in prenatal care. This method enables more precise genetic counseling and aids families facing a recurrent risk of fetal abnormalities in making informed reproductive decisions. To the best of our knowledge, this is the first study in Jordan to utilize prenatal WES for diagnosing fetal anomalies.
PMID:40721351 | DOI:10.1080/14767058.2025.2538208
