Abstract: SA-PO773
ADPKD and Collagen Genes (COL4A3, COL4A4, COL4A5)
Session Information
- Genetic Diseases: Cystic - Genetic Analysis and Extrarenal Manifestations
November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic
Authors
- Caprara, Carlotta, Ospedale San Bortolo di Vicenza, Vicenza, Veneto, Italy
- Corradi, Valentina, Ospedale San Bortolo di Vicenza, Vicenza, Veneto, Italy
- Rigato, Matteo, Ospedale San Bortolo di Vicenza, Vicenza, Veneto, Italy
- Mancini, Barbara, Ospedale San Bortolo di Vicenza, Vicenza, Veneto, Italy
- Marzano, Nenzi, Ospedale San Bortolo di Vicenza, Vicenza, Veneto, Italy
- Perbellini, Omar, Ospedale San Bortolo di Vicenza, Vicenza, Veneto, Italy
- Gastaldon, Fiorella, Ospedale San Bortolo di Vicenza, Vicenza, Veneto, Italy
- Ronco, Claudio, Ospedale San Bortolo di Vicenza, Vicenza, Veneto, Italy
- Zanella, Monica, Ospedale San Bortolo di Vicenza, Vicenza, Veneto, Italy
Background
The familial hematuria diseases are a heterogeneous group of monogenic conditions caused by mutations in one of the collagen IV genes: COL4A3/A4/A5 that are expressed in the glomerular basement membranes (GBM) and are responsible for the most frequent forms of microscopic hematuria (MH), Alport syndrome, and thin basement membrane nephropathy (TBMN).
Data suggest that about 1% of the world population may have MH and TBM, a frequency leads to occasional superimposition of TBMN with other glomerulopathies.
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a major genetic disorder affecting up to 12.5 million individuals worldwide and it is the fourth most common global cause for renal replacement therapy. Two are the principle causative genes: PKD1 and PKD2.
The aim of the study was to describe a cohort of clinically ADPKD patients (pts) studying collagen IV genes COL4A3/A4/A5.
Methods
We performed NGS with Sophia Genetic “Nephropathies Solution” Panel on clinically ADPKD pts. This panel includes 44 genes (target region 105.8kb) involved in different types of nephropathies.
We considered variants that are categorized as Vous, likely pathogenic or pathogenic (Class 3,4 or 5 of ACMG) in COL4A3, COL4A4 and COL4A5 genes.
Results
We found 13 (6.3%) clinically potentially interesting (Class 3,4 or 5 of ACMG) variants in collagen genes in 250 consecutive clinically ADPKD pts.
We found 2 pts PKD1, PKD2, PKHD1 negative: 1pt variations carrier COL4A4 NM_000092.5: c.2908C>T (p.Gln970Ter) and c.2756A>G (p.Glu919Gly); 1 pt carrier COL4A3 NM_000091.5: c.609+3_609+6del and COL4A5 NM_000495:c.169G>A p.(Gly57Arg).
We also found 4 pts with 4 Vous variants in collagen genes combine with at least 1 pathogenic or likely pathogenic variant in PKD1 or PKD2 genes.
We found 3 pts with likely pathogenic variants in COL4A4 or COL4A3 genes combined with Vous or likely benign variants in PKD1 or PKD2 genes and 1 pt with 1 variant likely pathogenic in COL4A3 and 1 likely pathogenic variant in PKD1.
Conclusion
The study outlines the importance to consider also collagen genes even if we have a clear clinical manifestation of ADPKD. Analysis of genes involved in these 2 pathologies could lead to better understand the phenotype-genotype correlation at least in patients with both conditions.