Chromosomal microarray analysis in fetuses with congenital anomalies of the kidney and urinary tract: A prospective cohort study and meta‐analysis

Abstract

Objective To evaluate the usefulness and incremental diagnostic yield of chromosomal microarray analysis (CMA) compared with standard karyotyping in fetuses with congenital anomalies of the kidney and urinary tract (CAKUT). Methods A prospective cohort study and systematic review of the literature were conducted. In the prospective cohort study, 123 fetuses with CAKUT, as detected by prenatal ultrasound at our center, were enrolled and evaluated using karyotyping and CMA. In the meta‐analysis, articles in PubMed and ISI Web of Knowledge databases describing copy number variations (CNVs) in prenatal cases of CAKUT were included. Results Among the 123 fetuses in our prospective cohort study, 13 fetuses were detected with chromosomal abnormalities or submicroscopic chromosomal abnormalities by both karyotyping and CMA. In the remaining 110 fetuses, four pathogenic CNVs in four fetuses were only detected by CMA, indicating an excess diagnostic yield of 3.6%. Six publications and our own study met the inclusion criteria for the meta‐analysis. In total, 615 fetuses with CAKUT were included. The pooled data from all of the reviewed studies indicate that the incremental yield of CMA over karyotyping was 3.8%. Conclusion The use of CMA provides a 3.8% incremental yield of detecting pathogenic CNVs in fetuses with CAKUT and normal karyotype.

Prenatal diagnosis of chromosomal aberrations by chromosomal microarray analysis in fetuses with ultrasound anomalies in the urinary system

“…We have shown that pCNVs are present in 13.64% (9/66) of fetuses with nonisolated urinary system anomalies; this frequency is comparable with the frequencies ranging from 9.5% to 19% reported in previous studies . Furthermore, the incremental yield of CMA over karyotyping of our study was similar to the result of previous meta‐analysis ( P > .05) . The detection rate in fetuses with nonisolated urinary system anomalies in this study was significantly higher than that in fetuses with isolated urinary system anomalies.…”

“…The highest detection rates for isolated urinary anomalies were observed in fetuses with echogenic kidneys (8/27, 29.63%), and 87.5% (7/8) of pCNVs in fetuses with echogenic kidneys was 17q12 deletion, which were similar to the previous studies . 17q12 recurrent deletion syndrome (MIM: 614527) is associated with RCAD syndrome, also known as maturity‐onset diabetes of young type 5 (MODY5) (MIM: 137920).…”

“…13,21,22 Furthermore, the incremental yield of CMA over karyotyping of our study was similar to the result of previous meta-analysis (P > .05). 14 The detection rate in fetuses with nonisolated urinary system anomalies in this study was significantly higher than that in fetuses with isolated urinary system anomalies.…”

“…To understand the roles of chromosomal abnormalities in fetuses with isolated genitourinary malformations over karyotyping, Shaffer et al performed a retrospective analysis of 115 fetuses, and Li et al performed a prospective of 87 fetuses and a meta‐analysis of 383 fetuses. The detection rates of pCNV were 5.2% and 3.8%, respectively.…”

Clinical Genetic Screening in Adult Patients with Kidney Disease

“…With hundreds of genes implicated, they are highly heterogeneous in both phenotype and genotype. In addition, these phenotypes are often caused by structural genomic variants (57), detectable by chromosomal microarray (58), whose diagnostic yield is greatest in patients with kidney parenchymal malformations and those with extrarenal manifestations (27,31,59). The remaining cases are caused by SNVs in a single gene, identifiable with exome sequencing or targeted panels, which can provide a diagnostic yield of around 14% in recent reports (3) and is slightly superior in syndromic cases (25% versus 9% [32], 23% versus 15% [31,60]) in pediatric and young adult cohorts.…”