Prenatal genetic diagnosis of Williams-Beuren syndrome with atypical and complex phenotypes using SNP array and whole exome sequencing

Author:

Liu weiqiang1ORCID,Cao Dingya2,Song Jinshuang1,Zhang Tong3,Zeng Shuxian1,Cong Xiaoyi1,Luo Xiaojin1,Hu Liang1,Pei Yuanyuan1,Chen Min2

Affiliation:

1. Longgang district maternity and child healthcare hospital

2. The Third Affiliated Hospital of Guangzhou Medical University

3. Longgang distirct maternity and child healthcare hospital

Abstract

Abstract

Background Williams-Beuren syndrome (WBS) is a severe congenital disorder. Prenatal diagnosis of WBS is difficult because the phenotypes of WBS fetuses are atypical or incomplete. This study used ultrasound, SNP array, and whole exome sequencing to analyze the association between genotype and complex phenotype in fetuses with WBS. Methods Chromosomal microarray analysis (CMA) and whole genome sequencing were performed in pregnant women with prenatal diagnosis. Genome-wide copy number variants (CNVs), regions of homozygosity (ROH), single nucleotide variants (SNVs), small insertions and deletions, and splice sites were analyzed. Results The 7q11.23 deletion was identified in seven fetuses out of 6718 prenatal diagnostic samples; ultrasound revealed that two fetuses had apparent cardiovascular anomalies; one fetus had persistent left superior vena cava and intrauterine growth retardation (IUGR). Two fetuses had polycystic kidney dysplasia, one of which was associated with a small amount of tricuspid regurgitation; the other two fetuses had no apparent ultrasound abnormalities. Detailed genetic analysis revealed CNVs ranging in size from 1.43 megabase pairs (Mb) to 1.66 Mb, affecting 34 to 41 genes, respectively. On average, 1.0 additional CNVs larger than 100 kilobase pairs of unknown significance and 0.43 ROH larger than 5 Mb were detected in these cases. The pathogenic or likely pathogenic SNV or splice site with the function of renal development and cardiovascular development was also identified in these cases. Conclusion The phenotype of WBS fetuses is atypical and complex, and the complex phenotype does not exclude association with other variants within the genome.

Publisher

Springer Science and Business Media LLC

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