The diagnostic efficacy of exome data analysis using fixed neurodevelopmental gene lists: Implications for prenatal setting

Rivka Sukenik-Halevy, Noa Ruhrman-Shahar, Naama Orenstein, Claudia Gonzaga-Jauregui, Alan R. Shuldiner, Nurit Magal, Ofir Hagari, Noy Azulay, Gabriel A. Lidzbarsky, Lily Bazak, Lina Basel-Salmon

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Objective: Laboratories performing prenatal exome sequencing (ES) frequently limit analysis to predetermined gene lists. We used a diagnostic postnatal ES cohort to assess how many of the genes diagnosed are not included in a number of select fixed lists used for prenatal diagnosis. Methods: Of 601 postnatal ES tests, pathogenic variants related to neurodevelopmental disorders were detected in 138 probands. We evaluated if causative genes were present in the following: (1) Developmental Disorders Genotype–Phenotype database list, (2) a commercial laboratory list for prenatal ES, (3) the PanelApp fetal anomalies panel, and (4) a published list used for prenatal diagnosis by ES (Prenatal Assessment of Genomes and Exomes study). Results: The percentages of cases where the diagnosed gene was not included in the selected four lists were; 11.6%, 17.24%, 23.2%, and 10.9%, respectively. In 13/138 (9.4%) cases, the causative gene was not included in any of the lists; in 4/13 (∼30%) cases noninclusion was explained by a relatively recent discovery of gene–phenotype association. Conclusions: A significant number of genes related to neurocognitive phenotypes are not included in some of the lists used for prenatal ES data interpretation. These are not only genes related to recently discovered disorders, but also genes with well-established gene–phenotype.

Original languageEnglish
Pages (from-to)701-707
Number of pages7
JournalPrenatal Diagnosis
Volume41
Issue number6
DOIs
StatePublished - May 2021
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2021 John Wiley & Sons Ltd.

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