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

Autor: Rivka Sukenik-Halevy, Noa Ruhrman-Shahar, Lina Basel-Salmon, Noy Azulay, Alan R. Shuldiner, Claudia Gonzaga-Jauregui, Ofir Hagari, Lily Bazak, Nurit Magal, Gabriel Arie Lidzbarsky, Naama Orenstein
Rok vydání: 2021
Předmět:
Zdroj: Prenatal Diagnosis. 41:701-707
ISSN: 1097-0223
0197-3851
DOI: 10.1002/pd.5929
Popis: 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.
Databáze: OpenAIRE
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