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. 2024 Sep;44(10):1179-1197.
doi: 10.1002/pd.6623. Epub 2024 Aug 13.

Prenatal exome sequencing, a powerful tool for improving the description of prenatal features associated with genetic disorders

Christel Thauvin-Robinet  1   2   3   4 , Aurore Garde  1   2 , Julian Delanne  1   2 , Caroline Racine  1   2 , Thierry Rousseau  5 , Emmanuel Simon  5 , Michel François  6 , Sebastien Moutton  1 , Odent Sylvie  7 , Chloe Quelin  7 , Godelieve Morel  7 , Alice Goldenberg  8 , Anne-Marie Guerrot  8 , Gabriella Vera  8 , Nicolas Gruchy  9 , Cindy Colson  10 , Odile Boute  10 , Carine Abel  11 , Audrey Putoux  12 , Jeanne Amiel  13 , Agnes Guichet  14 , Bertrand Isidor  15 , Caroline Deiller  16 , Constance Wells  16 , Caroline Rooryck  17 , Marine Legendre  17 , Christine Francannet  18 , Rodolphe Dard  19 , Sabine Sigaudy  20 , Ange-Line Bruel  2   3   4 , Hana Safraou  2   3   4 , Anne-Sophie Denommé-Pichon  2   3   4 , Sophie Nambot  1   2 , Marie-Laure Humbert Asensio  21 , Christine Binquet  21 , Yannis Duffourd  2   3   4 , Antonio Vitobello  2   3   4 , Christophe Philippe  2   3   4 , Laurence Faivre  1   2   3   4 , Frédéric Tran-Mau-Them  2   3   4 , Nicolas Bourgon  2   3   22
Affiliations

Prenatal exome sequencing, a powerful tool for improving the description of prenatal features associated with genetic disorders

Christel Thauvin-Robinet et al. Prenat Diagn. 2024 Sep.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT03964441.

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References

REFERENCES

    1. Liu L, Oza S, Hogan D, et al. Global, regional, and national causes of child mortality in 2000‐13, with projections to inform post‐2015 priorities: an updated systematic analysis. Lancet. 2015;385(9966):430‐440. https://doi.org/10.1016/s0140‐6736(14)61698‐6
    1. Hillman SC, McMullan DJ, Hall G, et al. Use of prenatal chromosomal microarray: prospective cohort study and systematic review and meta‐analysis. Ultrasound Obstet Gynecol. 2013;41(6):610‐620. https://doi.org/10.1002/uog.12464
    1. Mellis R, Oprych K, Scotchman E, Hill M, Chitty LS. Diagnostic yield of exome sequencing for prenatal diagnosis of fetal structural anomalies: a systematic review and meta‐analysis. Prenat Diagn. 2022;42(6):662‐685. https://doi.org/10.1002/pd.6115
    1. Tran Mau‐Them F, Delanne J, Denommé‐Pichon AS, et al. Prenatal diagnosis by trio exome sequencing in fetuses with ultrasound anomalies: a powerful diagnostic tool. Front Genet. 2023;14:1099995. https://doi.org/10.3389/fgene.2023.1099995
    1. Normand EA, Braxton A, Nassef S, et al. Clinical exome sequencing for fetuses with ultrasound abnormalities and a suspected Mendelian disorder. Genome Med. 2018;10(1):74. https://doi.org/10.1186/s13073‐018‐0582‐x

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