Next-Generation Sequencing (NGS) Analysis Illustrates the Phenotypic Variability of Collagen Type IV Nephropathies

Genes · 15 authors, 5 centres

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TL;DR

It found that mutations in these genes are linked to a wider spectrum of kidney abnormalities than traditionally recognized, including familial FSGS, cortical calcification, and multiple renal cysts.

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The authors focused on patients with unexpected clinical diagnoses and found a high prevalence of pathogenic variants in the COL4A4 and COL4A5 genes. Three representative cases are detailed: a case of familial focal segmental glomerulosclerosis (FSGS), a case of cortical calcification with end-stage renal disease, and a case of familial dysmorphic kidneys with multiple cysts.

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other

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nephrology

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ORIGINAL PAPER

PMC10048128

Next-Generation Sequencing (NGS) Analysis Illustrates the Phenotypic Variability of Collagen Type IV Nephropathies

Genes

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ABSTRACT

Abstract Mutations in COL4A3-A5 cause a spectrum of glomerular disorders, including thin basement membrane nephropathy (TBMN) and Alport syndrome (AS). The wide application of next-generation sequencing (NGS) in the last few years has revealed that mutations in these genes are not limited to these clinical entities. In this study, 176 individuals with a clinical diagnosis of inherited kidney disorders underwent an NGS-based analysis to address the underlying cause; those who changed or perfected the clinical diagnosis after molecular analysis were selected. In 5 out of 83 individuals reaching a molecular diagnosis, the genetic result was unexpected: three individuals showed mutations in collagen type IV genes. These patients showed the following clinical pictures: (1) familial focal segmental glomerulosclerosis; (2) end-stage renal disease (ESRD) diagnosed incidentally in a 49-year-old man, with diffuse cortical calcifications on renal imaging; and (3) dysmorphic and asymmetric kidneys with multiple cysts and signs of tubule–interstitial defects. Genetic analysis revealed rare heterozygote/compound heterozygote COL4A4-A5 variants. Our study highlights the key role of NGS in the diagnosis of inherited renal disorders and shows the phenotype variability in patients carrying mutations in collagen type IV genes. Keywords: basal membrane, COL4 , kidney disease, NGS

CITATION EXPORT

Miriam Zacchia, Giovanna Capolongo, Francesca Del Vecchio Blanco et al.. Next-Generation Sequencing (NGS) Analysis Illustrates the Phenotypic Variability of Collagen Type IV Nephropathies. Genes. (2023). https://doi.org/10.3390/genes14030764

AUTHORS

15 · 5 CENTRES

Miriam Zacchia, Giovanna Capolongo, Francesca Del Vecchio Blanco, Floriana Secondulfo, Neha Gupta, Giancarlo Blasio, Rosa Maria Pollastro, Angela Cervesato, Giulio Piluso, Giuseppe Gigliotti, Annalaura Torella, Vincenzo Nigro, Alessandra F Perna, Giovambattista Capasso, Francesco Trepiccione

1Department of Medical and Translational Sciences, University of Campania, Luigi Vanvitelli, 81100 Caserta, Italy
2Department of Precision Medicine, University of Campania, Luigi Vanvitelli, 81100 Caserta, Italy
3Biogem, Scarl, 83031 Ariano Irpino, Italy
4UOC Nefrologia e Dialisi, Ospedale Civile di Eboli “MM.SS. Addolorata”, 84025 Eboli, Italy
5Telethon Institute of Genetics and Medicine, 80078 Pozzuoli, Italy