Evaluation of Diagnostic Yield in Fetal Whole-Exome Sequencing: A Report on 45 Consecutive Families

Frontiers in Genetics

Aida M. Bertoli-Avella¹  Peter Bauer¹  Amihai Rigbi²  Ben Pode-Shakked³  Miriam Regev³  Annick Raas-Rothschild³  Elon Pras³  Michal Berkenstadt³  Lior Greenbaum³  Ortal Barel⁴  Hana Poran⁵  Michal Dicastro-Keidar⁵  Nurit Goldstein⁵  Anat Bar-Ziv⁵  Shlomit Eisenberg-Barzilai⁵  Haike Reznik-Wolf⁵ 

[1] Centogene AG, Rostock, Germany;Faculty of Education, Beit Berl College, Kfar Saba, Israel;Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;Sheba Cancer Research Center, Sheba Medical Center, Tel Hashomer, Israel;The Danek Gertner Institute of Human Genetics, Sheba Medical Center, Tel Hashomer, Israel;The Joseph Sagol Neuroscience Center, Sheba Medical Center, Tel Hashomer, Israel;

关键词: whole-exome sequencing (WES);    prenatal diagnosis;    ultrasound abnormalities;    clinical genetics;    congenital anomalies;   

DOI  :  10.3389/fgene.2019.00425

来源: DOAJ

【 摘 要 】

Prenatal ultrasound (US) abnormalities often pose a clinical dilemma and necessitate facilitated investigations in the search of diagnosis. The strategy of pursuing fetal whole-exome sequencing (WES) for pregnancies complicated by abnormal US findings is gaining attention, but the reported diagnostic yield is variable. In this study, we describe a tertiary center’s experience with fetal WES from both terminated and ongoing pregnancies, and examine the clinical factors affecting the diagnostic rate. A total of 45 consecutive families of Jewish descent were included in the analysis, for which clinical fetal WES was performed under either single (fetus only), trio (fetus and parents) or quatro (two fetuses and parents) design. Except one, all families were non-consanguineous. In 41 of the 45 families, WES was sought following abnormal fetal US findings, and 18 of them had positive relevant family history (two or more fetuses with US abnormalities, or single fetus with US abnormalities and an affected parent). The overall diagnostic yield was 28.9% (13/45 families), and 31.7% among families with fetal US abnormalities (13/41). It was significantly higher in families with prenatal US abnormalities and relevant family history (10/18, 55.6%), compared to families with prenatal US abnormal findings and lack of such history (3/23, 13%) (p = 0.004). WES yield was relatively high (42.9–60%) among families with involvement of brain, renal or musculoskeletal US findings. Taken together, our results in a real-world setting of genetic counseling demonstrates that fetal WES is especially indicated in families with positive family history, as well as in fetuses with specific types of congenital malformation.

【 授权许可】

Unknown