Abstract

Background: Williams-Beuren syndrome (WBS) is a severe congenital disorder that presents challenges in prenatal diagnosis due to the atypical or incomplete phenotypes exhibited by affected fetuses. This study investigated the relationship between genotype and complex phenotype in WBS fetuses using ultrasound, SNP array, and whole exome sequencing.
Methods: Chromosomal microarray analysis (CMA) and whole genome sequencing (WES) were conducted on pregnant women undergoing prenatal diagnosis. We analyzed genome-wide copy number variants (CNVs), regions of homozygosity (ROH), single nucleotide variants (SNVs), small insertions and deletions, and splice sites.
Results: A deletion at 7q11.23 was identified in 7 out of 6,718 prenatal diagnostic samples (1 in 960). Ultrasound findings varied: two fetuses exhibited cardiovascular anomalies; one presented with persistent left superior vena cava and intrauterine growth retardation (IUGR), while two others displayed polycystic kidney dysplasia, one accompanied by mild tricuspid regurgitation, and the remaining two fetuses showed no apparent ultrasound abnor-malities. Genetic analysis revealed CNVs ranging in size from 1.43 to 1.66 megabase pairs (Mb), affecting 34 to 41 genes. On average, one additional CNV larger than 100 kilobase pairs (Kb) of unknown significance and 0.43 ROH larger than 5 Mb were identified in these cases. Although pathogenic or likely pathogenic SNV or splice sites related to renal development and cardiovascular development were found, none correlated with the fetal phenotype observed.
Conclusions: The phenotypes of WBS fetuses are often atypical and complex. Future research should focus on integrating advanced genetic technologies and improved imaging modalities to enhance our understanding of the intricate genotype-phenotype relationships associated with WBS.

DOI: 10.7754/Clin.Lab.2024.241020