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Gene & Protein in Disease Alport syndrome: Genetics, variability, and management

been explored as a potential therapeutic tool in AS. In a Availability of data
study using urine-derived podocyte-lineage cells from AS
patients, the CRISPR/Cas9 application achieved correction Not applicable.
rates of 44 – 58%, reducing the proportion of indels References
in COL4A3 and COL4A5 mutations. The frequency of
unintended insertions or deletions remained below 15%. 59 1. De Gregorio V, Caparali EB, Shojaei A, Ricardo S, Barua M.
Alport syndrome: Clinical spectrum and therapeutic
Although these approaches demonstrate significant advances. Kidney Med. 2023;5(5):100631.
potential, their clinical application necessitates further doi: 10.1016/J.XKME.2023.100631
research to overcome challenges related to safety, efficacy,
and technical limitations. 2. Huang HX, Tsai IJ, Greenbaum LA. Alport syndrome:
Expanding diagnosis and treatment. Pediatr Neonatol.
7. Conclusion 2024;66:S13-S17.
AS is a complex genetic disease with a broad clinical spectrum doi: 10.1016/J.PEDNEO.2024.10.005
based on its genotype, and understanding its progression is 3. Puapatanakul P, Miner JH. Alport syndrome and Alport
fundamental to improving clinical care. Advances in genetic kidney diseases - elucidating the disease spectrum. Curr
testing have made it possible for an earlier diagnosis and Opin Nephrol Hypertens. 2024;33(3):283-290.
identification of specific variants, which can help guide doi: 10.1097/MNH.0000000000000983
treatment, family planning, and even prognosis. Nowadays, 4. Savige J. Heterozygous pathogenic COL4A3 and COL4A4
RAAS blockade remains the backbone of AS treatment, variants (autosomal dominant alport syndrome) are
although new therapy options are emerging. common, and not typically associated with end-stage kidney
SGLT2 inhibitors and experimental therapies, such as failure, hearing loss, or ocular abnormalities. Kidney Int
gene editing, which are more individualized. Progression Rep. 2022;7(9):1933-1938.
depends on the genetic variant, with XLAS and ARAS doi: 10.1016/J.EKIR.2022.06.001
causing earlier and more severe renal decline. Early 5. Gibson J, Fieldhouse R, Chan MMY, et al. Prevalence
diagnosis is critical for initiating effective treatment as estimates of predicted pathogenic col4a3-col4a5 variants in
early as possible. Continued research into AS’s genetic a population sequencing database and their implications for
causes, along with precision medicine, is key to improving alport syndrome. J Am Soc Nephrol. 2021;32(9):2273-2290.
disease management and patient quality of life.
doi: 10.1681/ASN.2020071065
Acknowledgments 6. Torra R, Lipska-Ziętkiewicz B, Acke F, et al. Diagnosis,
management and treatment of the Alport syndrome-2024
None.
guideline on behalf of ERKNet, ERA and ESPN. Nephrol
Funding Dial Transplant. 2014;16(3):518-524.
doi: 10.1093/NDT/GFAE265
None.
7. Gatseva A, Sin YY, Brezzo G, Van Agtmael T. Basement
Conflict of interest membrane collagens and disease mechanisms. Essays
Biochem. 2019;63(3):297-312.
The authors declare they have no competing interests.
doi: 10.1042/EBC20180071
Author contributions 8. Funk SD, Lin MH, Miner JH. Alport syndrome and pierson
Conceptualization: João Venda, Beatriz Ferreira syndrome: Diseases of the glomerular basement membrane.
Writing – original draft: João Venda, Beatriz Ferreira, Rita Matrix Biol. 2018;71-72:250.
Leal, Ana Galvão, Rui Alves doi: 10.1016/J.MATBIO.2018.04.008
Writing – review & editing: João Venda, Beatriz Ferreira, 9. Plaisier E, Gribouval O, Alamowitch S, et al. COL4A1
Andreia Henriques mutations and hereditary angiopathy, nephropathy,
aneurysms, and muscle cramps. N Engl J Med.
Ethics approval and consent to participate 2007;357(26):2687-2695.
Not applicable. doi: 10.1056/nejmoa071906

Consent for publication 10. Plaisier E, Ronco P. COL4A1-Related Disorders; 2016.
Available from: https://www.radiopaedia.org [Last accessed
Not applicable. on 2024 Dec 14].

Volume 4 Issue 2 (2025) 9 doi: 10.36922/gpd.7656