2017/11/30 by Maria Rasmussen, M. Rasmussen, Lone Sunde +28
Biochemistry, Genetics and Molecular Biology · Medicine · #Genetic Syndromes and Imprinting #Prenatal Screening and Diagnostics #Renal and related cancers
paper · pdf · doi:10.1111/cge.13185
openalex publication_date 2017/11/30 · crossref created 2017/11/30 · crossref issued 2018/02/23 · crossref published 2018/02/23 · crossref published-online 2018/02/23 · crossref published-print 2018/04/01 · crossref deposited 2023/09/10 · openalex created_date 2025/10/10 · crossref indexed 2026/07/28 · openalex updated_date 2026/08/01
Identification of fetal kidney anomalies invites questions about underlying causes and recurrence risk in future pregnancies. We therefore investigated the diagnostic yield of next-generation sequencing in fetuses with bilateral kidney anomalies and the correlation between disrupted genes and fetal phenotypes. Fetuses with bilateral kidney anomalies were screened using an in-house-designed kidney-gene panel. In families where candidate variants were not identified, whole-exome sequencing was performed. Genes uncovered by this analysis were added to our kidney panel. We identified likely deleterious variants in 11 of 56 (20%) families. The kidney-gene analysis revealed likely deleterious variants in known kidney developmental genes in 6 fetuses and TMEM67 variants in 2 unrelated fetuses. Kidney histology was similar in the latter 2 fetuses-presenting a distinct prenatal form of nephronophthisis. Exome sequencing identified ROBO1 variants in one family and a GREB1L variant in another family. GREB1L and ROBO1 were added to our kidney-gene panel and additional variants were identified. Next-generation sequencing substantially contributes to identifying causes of fetal kidney anomalies. Genetic causes may be supported by histological examination of the kidneys. This is the first time that SLIT-ROBO signaling is implicated in human bilateral kidney agenesis.