Evaluating the Clinical Utility of Genome Sequencing for Cytogenetically Balanced Chromosomal Abnormalities in Prenatal Diagnosis

Overview

Journal Front Genet

Date 2021 Feb 15

PMID 33584815

Citations 5

Authors

Mullin Ho Chung Yu

Jeffrey Fong Ting Chau

Sandy Leung Kuen Au

Hei Man Lo

Kit San Yeung

Jasmine Lee Fong Fung

Christopher Chun Yu Mak

Claudia Ching Yan Chung

Kelvin Yuen Kwong Chan

Brian Hon Yin Chung

Anita Sik Yau Kan

Affiliations

Soon will be listed here.

Abstract

Balanced chromosomal abnormalities (BCAs) are changes in the localization or orientation of a chromosomal segment without visible gain or loss of genetic material. BCAs occur at a frequency of 1 in 500 newborns and are associated with an increased risk of multiple congenital anomalies and/or neurodevelopmental disorders, especially if it is a mutation. In this pilot project, we used short read genome sequencing (GS) to retrospectively re-sequence ten prenatal subjects with BCAs and compared the performance of GS with the original karyotyping. GS characterized all BCAs found by conventional karyotyping with the added benefit of precise sub-band delineation. By identifying BCA breakpoints at the nucleotide level using GS, we found disruption of OMIM genes in three cases and identified cryptic gain/loss at the breakpoints in two cases. Of these five cases, four cases reached a definitive genetic diagnosis while the other one case had a BCA interpreted as unknown clinical significance. The additional information gained from GS can change the interpretation of the BCAs and has the potential to improve the genetic counseling and perinatal management by providing a more specific genetic diagnosis. This demonstrates the added clinical utility of using GS for the diagnosis of BCAs.

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