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Exome sequencing for structurally normal fetuses-yields and ethical issues.

ABSTRACT: The yield of chromosomal microarray analysis (CMA) is well established in structurally normal fetuses (0.4-1.4%). We aimed to determine the incremental yield of exome sequencing (ES) in this population. From February 2017 to April 2022, 1,526 fetuses were subjected to ES; 482 of them were structurally normal (31.6%). Only pathogenic and likely pathogenic (P/LP) variants, per the American College of Medical Genetics and Genomics (ACMG) classification, were reported. Additionally, ACMG secondary findings relevant to childhood were reported. Four fetuses (4/482; 0.8%) had P/LP variants indicating a moderate to severe disease in ATP7B, NR2E3, SPRED1 and FGFR3, causing Wilson disease, Enhanced S-cone syndrome, Legius and Muenke syndromes, respectively. Two fetuses had secondary findings, in RET and DSP. Our data suggest that offering only CMA for structurally normal fetuses may provide false reassurance. Prenatal ES mandates restrictive analysis and careful management combined with pre and post-test genetic counseling.

SUBMITTER: Daum H

PROVIDER: S-EPMC9905544 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Exome sequencing for structurally normal fetuses-yields and ethical issues.

Daum Hagit H Harel Tamar T Millo Talya T Eilat Avital A Fahham Duha D Gershon-Naamat Shiri S Basal Adily A Rosenbluh Chaggai C Yanai Nili N Porat Shay S Kabiri Doron D Yagel Simcha S Valsky Dan V DV Elpeleg Orly O Meiner Vardiella V Mor-Shaked Hagar H

European journal of human genetics : EJHG 20220907 2

The yield of chromosomal microarray analysis (CMA) is well established in structurally normal fetuses (0.4-1.4%). We aimed to determine the incremental yield of exome sequencing (ES) in this population. From February 2017 to April 2022, 1,526 fetuses were subjected to ES; 482 of them were structurally normal (31.6%). Only pathogenic and likely pathogenic (P/LP) variants, per the American College of Medical Genetics and Genomics (ACMG) classification, were reported. Additionally, ACMG secondary f ...[more]

PMID: 36071243

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Exome sequencing for structurally normal fetuses-yields and ethical issues.

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Exome sequencing for structurally normal fetuses-yields and ethical issues.

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