Targeted next‐generation sequencing in a large series of fetuses with severe renal diseases

Jordan, Penelope; Dorval, Guillaume; Arrondel, Christelle; Morinière, Vincent; Tournant, Carole; Audrézet, Marie-Pierre; Michel-Calemard, Laurence; Putoux, Audrey; Lesca, G.; Labalme, Audrey; Whalen, Sandra; Lœuillet, Laurence; Martinovic, Jéléna; Attié‐Bitach, Tania; Bessières, Bettina; Schaefer, Élise; Scheidecker, Sophie; Lambert, Laëtitia; Bénéteau, Claire; Patat, Olivier; Boute-Benejean, Odile; Molin, Arnaud; Guimiot, Fabien; Fontanarosa, Nicolas; Nizon, Mathilde; Lefebvre, Mathilde; Jeanpierre, C.; Saunier, Sophie; Heidet, Laurence

doi:10.1002/humu.24324

Cited by 14 publications

(20 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, one patient in this pooled exome study with a compound heterozygous mutation in FRAS1 had a sibling with previous intrauterine demise secondary to bilateral renal agenesis, suggesting various FRAS1 mutations may cause more severe renal phenotypes. This is further supported by a recent publication identifying biallelic FRAS1 variants in four cases of bilateral renal agenesis (34).…”

Section: Discussionsupporting

confidence: 71%

Whole Exome Sequencing in a Population With Severe Congenital Anomalies of Kidney and Urinary Tract

et al. 2022

View full text Add to dashboard Cite

Fetal and neonatal interventions (e.g., amnioinfusions, amniotic shunting, and infant dialysis) have increased survival of infants with severe Congenital Anomalies of the Kidney and Urinary Tract (CAKUT), however, outcomes vary dramatically. Our aim was to perform Whole Exome Sequencing (WES) in a unique severe CAKUT population with the goal to identify new variants that will enhance prediction of postnatal outcomes. We performed trio WES on five infants with severe CAKUT (undergoing fetal interventions and/or those who initiated renal replacement therapy (RRT) within 1 month of life) and their parents as well as three singletons. We identified three potential candidate gene variants (NSUN7, MTMR3, CEP162) and validated two variants in known CAKUT genes (GATA3 and FRAS1) showing strong enrichment in this severe phenotype population. Based on our small pilot study of a unique severe CAKUT population, WES appears to be a potential tool to help predict the course of infants with severe CAKUT prenatally.

show abstract

Section: Discussionsupporting

confidence: 71%

Whole Exome Sequencing in a Population With Severe Congenital Anomalies of Kidney and Urinary Tract

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In model organisms mutations of mouse Bicc1 as well as morpholino disruption of Xenopus and zebrafish Bicc1 orthologs in developing embryos result in cystic kidneys ( Cogswell et al, 2003 ; Tran et al, 2007 , 2010 ; Bouvrette et al, 2010 ) that closely resemble the defects due to PKD. Specific BICC1 mutations have been identified in a small number of human patients with cystic kidney dysplasia ( Kraus et al, 2012 ) as well as a cohort of fetuses affected with severe renal defects ( Jordan et al, 2022 ).…”

Section: Human Bicc1 and Clinical Associationsmentioning

confidence: 99%

Bicaudal-C Post-transcriptional regulator of cell fates and functions

Dowdle

Kanzler²,

Harder³

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Bicaudal-C (Bicc1) is an evolutionarily conserved RNA binding protein that functions in a regulatory capacity in a variety of contexts. It was originally identified as a genetic locus in Drosophila that when disrupted resulted in radical changes in early development. In the most extreme phenotypes embryos carrying mutations developed with mirror image duplications of posterior structures and it was this striking phenotype that was responsible for the name Bicaudal. These seminal studies established Bicc1 as an important regulator of Drosophila development. What was not anticipated from the early work, but was revealed subsequently in many different organisms was the broad fundamental impact that Bicc1 proteins have on developmental biology; from regulating cell fates in vertebrate embryos to defects associated with several human disease states. In the following review we present a perspective of Bicc1 focusing primarily on the molecular aspects of its RNA metabolism functions in vertebrate embryos.

show abstract

“…Department of Necker University Hospital (Paris, France) as in Jordan et al, 2022. 8 A panel of 240 unique genes involved in monogenic renal diseases including genes of Alport Syndrome and podocytopathies, ciliopathies, Autosomal Dominant Tubulo-Interstitial Kidney Disease, renal tubular dysgenesis and CAKUT was used for the genetic screening (See Table S1). MUC1 was not included in that panel, as the predominant MUC1 frameshift variant is usually not detected by short read sequencing.…”

Section: Genetic Analysis Was Performed In the Molecular Geneticsmentioning

confidence: 99%

“…5 To date, pathogenic variants in only a few genes (ITGA8, GREB1L, FGF20, EYA1, HNF1B, FRAS1, GFRA, NPNT, and ANOS1) have been shown to cause renal agenesis in humans. [6][7][8] Integrin Subunit Alpha 8 gene (ITGA8, OMIM * 604063) encodes an integrin chain which is predominantly expressed on mesenchymal cells. 9 Itga8 is known to have a major role in kidney development, as it takes part in the epithelial-mesenchymal interactions required for kidney organogenesis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bi‐allelic pathogenic variants in ITGA8 cause slowly progressive renal disease of unknown etiology

Gómez-Conde

Dunand

Hummel³

et al. 2022

Clinical Genetics

Self Cite

View full text Add to dashboard Cite

Integrin Subunit Alpha 8 gene (ITGA8) encodes an integrin chain that is known to be critical in the early stage of the kidney development. Bi‐allelic pathogenic variants in ITGA8 are associated with bilateral renal agenesis, as well as anomalies involving urogenital system. Here, we report two unrelated patients presenting with slowly progressing chronic kidney disease associated with bilateral renal hypodysplasia carrying homozygous loss of function variants in the ITGA8 gene. These results broaden the clinical and genotypic spectrum of ITGA8 defects, revealing the high and unexpected degree of phenotypic heterogeneity of this autosomal recessive disease. Our study emphasizes the usefulness of Next‐Generation Sequencing in unraveling the genetic cause of chronic kidney disease of unknown etiology, and raises the question of genetic modifiers involved in the variation of the phenotypes associated with autosomal recessive ITGA8 pathogenic variants.

show abstract

Targeted next‐generation sequencing in a large series of fetuses with severe renal diseases

Abstract: We report the screening of a large panel of genes in a series of 100 fetuses (98 families) affected with severe renal defects. Causative variants were identified in

Cited by 14 publications

References 31 publications

Whole Exome Sequencing in a Population With Severe Congenital Anomalies of Kidney and Urinary Tract

Whole Exome Sequencing in a Population With Severe Congenital Anomalies of Kidney and Urinary Tract

Bicaudal-C Post-transcriptional regulator of cell fates and functions

Bi‐allelic pathogenic variants in ITGA8 cause slowly progressive renal disease of unknown etiology

Contact Info

Product

Resources

About