Analytical validity and clinical utility of whole-genome sequencing for cytogenetically balanced chromosomal abnormalities in prenatal diagnosis: abridged secondary publication
BHY Chung1,2, ASY Kan2,3, KYK Chan2,3, W Yang1, MHY Tang2,3, CCY Mak1, GKC Leung1
1 Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong
2 Department of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong Kong
3 Prenatal Diagnostic Laboratory, Department of Obstetrics and Gynaecology, Tsan Yuk Hospital
1. Whole-genome sequencing was superior to conventional karyotyping in detection of banding in nine of 10 cases. Improvement in detection could be confirmed by orthogonal methods.
2. Gene disruption was identified in two cases and led to definitive diagnoses for two families with proband affected by X-linked epilepsy (disruption of PCDH19) or microcephalic osteodysplastic primordial dwarfism type II (MOPDII). In the third case, gene disruption was identified, but variant of uncertain significance was concluded.
3. Using both short read (Illumina) and long read (Nanopore & PacBio) sequencing data together with bioinformatics tool (WhatsHap) can detect additionally the phasing of mutations.
4. Understanding the genomic mechanism of gene disruption secondary to balanced chromosomal abnormalities can guide the genetic counselling. It allows accurate and personalised disease risk prediction.