Mutations in the genes COL4A3, COL4A4, and COL4A5 affect the synthesis, assembly, deposition, or function of the collagen IV α345 molecule, the major collagenous constituent of the mature mammalian glomerular basement membrane. These mutations are associated with a spectrum of nephropathy, from microscopic hematuria to progressive renal disease leading to ESRD, and with extrarenal manifestations such as sensorineural deafness and ocular anomalies. The existing nomenclature for these conditions is confusing and can delay institution of appropriate nephroprotective therapy. Herein we propose a new classification of genetic disorders of the collagen IV α345 molecule with the goal of improving renal outcomes through regular monitoring and early treatment.
Bibliographical noteFunding Information:
The French Alport Registry is supported by the French Association for the Information and Research on Genetic Renal Diseases (AIRG-France), the National database on Rare Diseases (BNDMR; http://www.bndmr.fr ), and the Rare Disease Cohorts (RADICO; http://www.radico.fr/fr/ ) and participates in the ATHENA study sponsored by Regulus Therapeutics.
The Italian registry of Alport syndrome is supported by Italian Association of Alport Syndrome (ASAL; www.asalonlus.it ) by donations in favor of Graziano and Marco Laurini and the correlated biobank is within the Telethon Network of Genetics Biobanks (TNGB; project no. GTB12001).
The Alport Syndrome Treatments and Outcomes Registry (ASTOR) is supported by the Alport Syndrome Foundation, the Kenneth and Claudia Silverman Family Foundation, and the Schuman and Pedersen families. ASTOR participates in the ATHENA and Study of RG-012 in Male Subjects With Alport Syndrome (HERA) studies sponsored by Regulus Therapeutics and the Phase 2/3 Trial of the Efficacy and Safety of Bardoxolone Methyl in Patients With Alport Syndrome (CARDINAL) study sponsored by Reata Pharmaceuticals and receives research support from Novartis Institute for Biomedical Research.
© 2018 International Society of Nephrology
- Alport syndrome
- chronic kidney disease