Alex Chang, MD (@alexchangmd.bsky.social)

Prenatal diagnosis of fetuses w/renal abnormalities: 9.4% with chromosomal abnormalities. Most common 17q12 syndrome (large deletion encompasses HNF1B), then ciliary genes (TMEM67, NPHP3, CEP290, BBS2, TTC8). WES further revealed more diagnoses (15.8%). ojrd.biomedcentral.com/articles/10....

loading . . .

Prenatal diagnosis of fetuses with renal abnormalities: a retrospective analysis of 329 Chinese cases - Orphanet Journal of Rare Diseases Background There is no clear guidance on prenatal diagnostic testing strategies for congenital renal anomalies. Therefore, this study aims to investigate the retrospective analysis of ultrasound and genetic diagnostic results in cases of fetal renal abnormalities and to establish genotype-phenotype correlations. Methods A total of 329 fetuses with renal abnormalities that underwent prenatal diagnostic testing from January 2020 to April 2023 were recruited in this study. These cases were classified into 11 subgroups based on their ultrasound diagnosis. All cases underwent chromosomal microarray analysis (CMA) or copy number variation sequencing (CNV-seq), with subsequent whole exome sequencing (WES) conducted on select CMA/CNV-seq negative cases, subject to parental consent for further testing targeting monogenic variations. Results Of the 329 cases analyzed, CMA/CNV-seq detected chromosomal abnormalities in 31 cases, with a detection rate of 9.4% (31/329). The most common abnormality was 17q12 deletion, accounting for 29% of the positive cases (9/31) and 2.7% of the total cases (9/329). WES was conducted on 76 cases (76/298, 25.5%), revealing 16 monogenic variants, and 2 CNVs in 12 cases (15.8%). An overall positive diagnostic yield of 13.1% (43/329) was obtained in the pipeline of combinational CMA/CNV-seq and WES analysis. Ciliary genes (TMEM67, NPHP3, CEP290, BBS2, and TTC8) were frequently implicated by WES. Several genotype-phenotype correlations emerged, including (1) hyperechogenic kidneys associated with 17q12 deletion, (2) renal dysplasia, renal cysts, hydronephrosis, ectopic kidney, and renal duplication with chromosomal abnormalities, (3) unilateral renal agenesis and polycystic kidneys with monogenic variants. Conclusion This study reveals genotype-phenotype correlations in fetal renal abnormalities, informing prenatal counseling regarding diagnostic testing options and expected outcomes. https://ojrd.biomedcentral.com/articles/10.1186/s13023-025-04001-x