Hong Kong Med J 2025;31(Suppl 7):S13-7
Mate-pair low-pass genome sequencing for prenatal diagnosis of fetuses with ultrasound anomalies: abridged secondary publication
Z Dong1, TY Leung1, IFM Lo2, YKY Kwok1,2
1 Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China
2 Clinical Genetic Service, Department of Health, Hong Kong SAR, China
 
 
  1. DNA from 400 fetuses with ultrasound anomalies was examined using chromosomal microarray analysis (CMA) and low-pass mate-pair genome sequencing (GS) to identify clinically significant copy-number variants (CNVs), structural variants, and regions with absence of heterozygosity
  2. CMA and low-pass mate-pair GS reported diagnostic yields of 8.5% and 10.3%, respectively.
  3. Low-pass mate-pair GS additionally identified cryptic CNVs (n=4) and mosaic CNVs (n=2), and reclassified 12 (60%) of 20 variants of uncertain significance identified by CMA.
  4. Low-pass mate-pair GS classified 14 structural variants as variants of uncertain significance due to the unavailability of cultured cells for RNA sequencing or inconclusive RNA sequencing results in the submitted samples.
  5. Low-pass mate-pair GS can serve as an alternative for the confirmation of fetal ultrasound anomalies.