Details

Autor(en) / Beteiligte

• Filer, Dayne L.
• Mieczkowski, Piotr A.
• Brandt, Alicia
• Gilmore, Kelly L.
• Powell, Bradford C.
• Berg, Jonathan S.
• Wilhelmsen, Kirk C.
• Vora, Neeta L.

Titel

Noninvasive prenatal exome sequencing diagnostic utility limited by sequencing depth and fetal fraction

Ist Teil von

• Prenatal diagnosis, 2022-05, Vol.42 (5), p.567-573

Ort / Verlag

England: Wiley Subscription Services, Inc

Erscheinungsjahr

2022

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• Objective Sequencing cell‐free DNA now allows detection of large chromosomal abnormalities and dominant Mendelian disorders in the prenatal period. Improving upon these methods would allow newborn screening programs to begin with prenatal genetics, ultimately improving the management of rare genetic disorders. Methods As a pilot study, we performed exome sequencing on the cell‐free DNA from three mothers with singleton pregnancies to assess the viability of broad sequencing modalities in a noninvasive prenatal setting. Results We found poor resolution of maternal and fetal genotypes due to both sampling and technical issues. Conclusion We find broad sequencing modalities inefficient for noninvasive prenatal applications. Alternatively, we suggest a more targeted path forward for noninvasive prenatal genotyping. Key points What’s already known about this topic? Sequencing‐based noninvasive testing detects large copy number abnormalities and some single‐gene disorders. Fetal exome sequencing (ES) provides 10%–20% diagnostic yield for structural abnormalities after normal karyotype and microarray. What does this study add? Cell‐free ES in three gravid patients with suspected genetic disease in the fetus. Discussion of probability theory underlying noninvasive fetal genotyping. We demonstrate broad sequencing approaches are limited by sampling and technical difficulties, concluding broad sequencing is currently inappropriate for noninvasive testing.