Copy number variations associated with fetal congenital kidney malformations

Meiying Cai; Na Lin; Linjuan Su; Xiaoqing Wu; Xiaorui Xie; Ying Li; Xuemei Chen; Yuan Lin; Hailong Huang; Liangpu Xu

doi:10.1186/s13039-020-00481-7

Copy number variations associated with fetal congenital kidney malformations

Mol Cytogenet. 2020 Mar 24:13:11. doi: 10.1186/s13039-020-00481-7. eCollection 2020.

Authors

Meiying Cai^#¹, Na Lin^#¹, Linjuan Su¹, Xiaoqing Wu¹, Xiaorui Xie¹, Ying Li¹, Xuemei Chen¹, Yuan Lin¹, Hailong Huang¹, Liangpu Xu¹

Affiliation

¹ Department of the Prenatal Diagnosis Center, Fujian Provincial Maternity and Children's Hospital, affiliated hospital of Fujian Medical University, Fujian Key Laboratory for Prenatal Diagnosis and Birth Defect, Fuzhou, China.

^# Contributed equally.

Abstract

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) constitute 20-30% of all congenital malformations. Within the CAKUT phenotypic spectrum, renal hypodysplasia (RHD) is particularly severe. This study aimed to evaluate the applicability of single-nucleotide polymorphism (SNP) array test in prenatal diagnosis of RHD for improving prenatal genetic counseling and to search for evidence of a possible causative role of copy-number variations (CNVs) in RHD.

Results: We performed a systematic survey of CNV burden in 120 fetuses with RHD: 103 cases were isolated RHD and 17 were non-isolated RHD. Single-nucleotide polymorphism (SNP) array test was performed using the Affymetrix CytoScan HD platform. All annotated CNVs were validated by fluorescence in situ hybridization. We identified abnormal CNVs in 15 (12.5%) cases of RHD; of these CNVs, 11 were pathogenic and 4 were variants of uncertain significance. The detection rate of abnormal CNVs in non-isolated RHD was higher (29.4%, 5/17) than that in isolated RHD (9.7%, 10/103) (P = 0.060). Parents are more inclined to terminate the pregnancy if the fetuses have pathogenic results of the SNP-array test.

Conclusions: The variable phenotypes that abnormal CNVs may cause indicate the genetic counseling is needed for RHD cases.

Keywords: Chromosomal microarray analysis; Copy-number variations; Etiology; Renal hypodysplasia.