Retrospectif evaluation of whole exome analysis (WES) diagnotic yeild in fetuses with major and/or structural anomalies

Prenatal WES has started to take place more frequently in the literature in 2016 and later, has been studied on cases with different number of participants and different phenotypic findings, and therefore the diagnostic power is at varying rates in the literature,ranging from 15% to 42%. While the publications reported in the literature so far were conducted in societies with low prevalence of consanguineous marriage and with cases with low positive family history, our study was composed of 20 cases, 50% of whom had parental consanguineous marriage and 25% of whom had a positive family history, due to population characteristics. It is one of the very first examples in the literature with high consanguinity rates and in which postnatal evaluations and follow-up of cases are made. In our study, in 9 of 20 cases in which chromosomal anomalies that would explain the clinic were excluded, genetic etiology was found to explain the fetal phenotype with whole-exome sequencing, and the diagnosis rate of prenatal whole exome sequencing analysis was found as 45%. It was thought that the rate of diagnosis was higher than the literature rates, due to the high rate of inter-parental consanguinity and similarly affected individuals in families. The highest diagnostic yield of WES analysis was obtained in fetuses with fetal akinesia, central nervous system anomalies and skeletal system involvement. In addition, in contrast to the high sporadic rates in the literature, it has been shown that all posterior encephalocele cases included in our study are syndromic and caused by monogenic genetic etiologies, thus paving the way for planning prenatal whole-exome sequencing studies in encephalocele cases. Our study is the first prenatal exome sequencing study studied in the Turkish population to the best of our knowledge. With the results, the diagnostic yield of exome sequencing has been demonstrated in our society where consanguineous marriage is common, and its applicability in our society has been questioned.