Copy number variations associated with fetal congenital kidney malformations

• Published in: Molecular cytogenetics Vol. 13; no. 1; p. 11
• Main Authors: Cai, Meiying, Lin, Na, Su, Linjuan, Wu, Xiaoqing, Xie, Xiaorui, Li, Ying, Chen, Xuemei, Lin, Yuan, Huang, Hailong, Xu, Liangpu
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24.03.2020; BioMed Central; BMC
• Subjects: Amniocentesis; Analysis; Biotechnology industries; Birth defects; Chromosomal microarray analysis; Congenital defects; Congenital diseases; Copy number; Copy-number variations; Criminal investigation; Defects; Development and progression; DNA microarrays; EDTA; Etiology; Etiology (Medicine); Fetuses; Fluorescence; Fluorescence in situ hybridization; Genes; Genetic counseling; Genetic disorders; Genetic polymorphisms; High definition television; Kidney diseases; Kidneys; Medical genetics; Parents & parenting; Phenotypes; Polymorphism; Pregnancy; Pregnant women; Prenatal diagnosis; Renal hypodysplasia; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Statistical analysis; Studies; Surveys; Ultrasonic imaging; Urinary tract; Urogenital system; United States; Renal hypodysplasia; Chromosomal microarray analysis; Etiology; Copy-number variations
• ISSN: 1755-8166; 1755-8166
• DOI: 10.1186/s13039-020-00481-7

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. 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) (  = 0.060). Parents are more inclined to terminate the pregnancy if the fetuses have pathogenic results of the SNP-array test. The variable phenotypes that abnormal CNVs may cause indicate the genetic counseling is needed for RHD cases.