Abstract - Text

Abstract-Text

In recent years, next generation sequencing (NGS) has become the standard for identifying the causes of genetic diseases. Trio exome analysis is particularly invaluable in solving syndromic cases. The solution rate for trios is about 37%, compared to 21% for the single exome. The trio considerably simplifies the identification of causative variants by comparing the sequence information with data obtained for the parents and allows, for example, the discovery of de novo variants.

However, in addition to the possibilities of the prenatal trio, there are also many challenges, such as a short turnaround time, patient"s acceptance, incidental findings with medical relevance for the parents, interpretation of unclear variants, as well as ethical and psychosocial issues.

Here we present an update on prenatal trio analyses; more than 800 cases over the course of the last three years with a solution rate of approximately 1/3 of cases. In addition to sequence variants with the expected inheritance patterns and a high proportion of de novo variants, mitochondrial variants, low-grade mosaicism, chromosomal alterations (gains, losses, structural variants) and uniparental disomies were detected. We also compared solution rates of different disease groups/ fetal anomalies. As expected, fetal skeletal malformations resulted in the highest percentage of solved cases, but causative variants were also found for a large proportion of cases with soft markers.

Overall, our results highlight the diagnostic value of prenatal trio exome analysis in the investigation of genetic causes for fetal anomalies.