@article{f32b435399914ed1b0e0a213aed0f58f,
title = "Exome sequencing as first-tier test for fetuses with severe central nervous system structural anomalies",
abstract = "Objective: Prenatally detected central nervous system (CNS) anomalies present a diagnostic challenge. In this study, we compared the diagnostic yield of exome sequencing (ES) and chromosomal microarray analysis (CMA) in fetuses with a major CNS anomaly. Methods: This was a retrospective study of 114 cases referred for genetic evaluation following termination of pregnancy (TOP) due to a major CNS anomaly detected on prenatal ultrasound. All fetuses were first analyzed by CMA. All CMA-negative cases were offered ES. CMA-positive cases were reanalyzed using ES to assess its ability to detect copy-number variants (CNVs). Results: CMA identified a pathogenic or likely pathogenic (P/LP) CNV in 11/114 (10%) cases. Eighty-six CMA-negative cases were analyzed using ES, which detected P/LP sequence variants in 38/86 (44%). Among recurrent cases (i.e. cases with a previously affected pregnancy), the incidence of P/LP sequence variants was non-significantly higher compared with non-recurrent ones (12/19 (63%) vs 26/67 (39%); P = 0.06). Among the 38 cases with an ES diagnosis, 20 (53%) were inherited and carried a significant risk of recurrence. Reanalysis of 10 CMA-positive cases by ES demonstrated that the bioinformatics pipeline used for sequence variant analysis also detected all P/LP CNVs, as well as three previously known non-causative CNVs. Conclusions: In our study, ES provided a high diagnostic yield (> 50%) in fetuses with severe CNS structural anomalies, which may have been partly due to the highly selected case series that included post-TOP cases from a specialist referral center. These data suggest that ES may be considered as a first-tier test for the prenatal diagnosis of major fetal CNS anomalies, detecting both P/LP sequence variants and CNVs. This is of particular importance given the time constraints of an ongoing pregnancy and the risk of recurrence in future pregnancies.",
keywords = "brain, central nervous system, chromosomal microarray, copy-number variant, exome sequencing, fetus, malformation, prenatal diagnosis",
author = "Y. Yaron and {Ofen Glassner}, V. and A. Mory and {Zunz Henig}, N. and A. Kurolap and {Bar Shira}, A. and {Brabbing Goldstein}, D. and D. Marom and {Ben Sira}, L. and {Baris Feldman}, H. and G. Malinger and {Krajden Haratz}, K. and A. Reches",
note = "Publisher Copyright: {\textcopyright} 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.",
year = "2022",
month = jul,
doi = "10.1002/uog.24885",
language = "אנגלית",
volume = "60",
pages = "59--67",
journal = "Ultrasound in Obstetrics and Gynecology",
issn = "0960-7692",
publisher = "John Wiley and Sons Ltd",
number = "1",
}