Prenatal Exome Sequencing Leads to Molecular Diagnoses For Subset of Fetal Structural Anomaly Cases

For a paper appearing in Genome Medicine, a team led by investigators at Guangzhou Medical University presents an exome sequencing-based approach for diagnosing fetal structural anomalies prenatally. Using trio exome sequencing, the researchers retrospectively profiled 565 fetuses showing anomalies by ultrasound without clear molecular explanations for these anomalies by chromosomal microarray or karyotyping analyses. Based on findings in that cohort, they went on to apply a similar prenatal exome sequencing strategy in 1,053 prospective cases, ultimately reaching molecular diagnoses in more than 14 percent of the 1,618 cases with genotype-driven analyses, phenotype-driven analyses, and new analyses performed as more data became available. The approach led to diagnoses in more than 30 percent of the fetuses with skeletal abnormalities and nearly 26 percent of the cases marked by multiple organ changes, but did not lead to diagnoses in any chest abnormality cases, the authors report, noting that their results expanded the phenotypes linked to dozens of genes. Their study, they conclude, demonstrated that prenatal exome sequencing "clearly improves existing prenatal diagnostic capabilities, expands our understanding of genetic disease in utero, and thus helps us to better interpret fetal phenotypes in the future."