Thauvin‐Robinet, Christel, Garde, Aurore, Delanne, Julian, Racine, Caroline, Rousseau, Thierry, Simon, Emmanuel, François, Michel, Moutton, Sebastien, Sylvie, Odent, Quelin, Chloe, Morel, Godelieve, Goldenberg, Alice, Guerrot, Anne‐Marie, Vera, Gabriella, Gruchy, Nicolas, Colson, Cindy, Boute, Odile, Abel, Carine, Putoux, Audrey, and Amiel, Jeanne
Objective: Prenatal exome sequencing (pES) is now commonly used in clinical practice. It can be used to identifiy an additional diagnosis in around 30% of fetuses with structural defects and normal chromosomal microarray analysis (CMA). However, interpretation remains challenging due to the limited prenatal data for genetic disorders. Method: We conducted an ancillary study including fetuses with pathogenic/likely pathogenic variants identified by trio‐pES from the "AnDDI‐Prenatome" study. The prenatal phenotype of each patient was categorized as typical, uncommon, or unreported based on the comparison of the prenatal findings with documented findings in the literature and public phenotype‐genotype databases (ClinVar, HGMD, OMIM, and Decipher). Results: Prenatal phenotypes were typical for 38/56 fetuses (67.9%). For the others, genotype‐phenotype associations were challenging due to uncommon prenatal features (absence of recurrent hallmark, rare, or unreported). We report the first prenatal features associated with LINS1 and PGM1 variants. In addition, a double diagnosis was identified in three fetuses. Conclusion: Standardizing the description of prenatal features, implementing longitudinal prenatal follow‐up, and large‐scale collection of prenatal features are essential steps to improving pES data interpretation. Key points: What's already known about this topic? Prenatal exome sequencing detects an additional diagnosis in approximately 30% of fetuses with structural defects and normal chromosomal microarray analysis.Prenatal phenotyping may be challenging (limited examination of some organs, functional changes at birth, no intellectual or sensory information).Genetic disorders are highly heterogeneous. What does this study add? In 67.9% of cases, the association between the fetal phenotype and a relevant variant was straightforward. Conversely, it was challenging in 32.1% of cases due to unreported or uncommon prenatal findings.We reported prenatal findings associated with bi‐allelic LINS1 and PGM1 variants.Collaborative compilation of prenatal findings related to genetic disorders may lead to better understanding and identification of fetal conditions. [ABSTRACT FROM AUTHOR]