Missense mutation (Ser654Leu) in the <em>ITGA8</em> gene associated with renal hypodysplasia: A case report

Singh,Kumar Gautam; Moorthy,Anbalagan

doi:10.3892/br.2025.1946

Missense mutation (Ser654Leu) in the ITGA8 gene associated with renal hypodysplasia: A case report

Authors:
- Kumar Gautam Singh
- Anbalagan Moorthy
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Affiliations: Vellore Institute of Technology, Vellore Campus, Vellore, Tamil Nadu 632014, India
Published online on: February 17, 2025 https://doi.org/10.3892/br.2025.1946
Article Number: 68
Copyright: © Singh et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Renal hypodysplasia is a congenital kidney anomaly that occurs when part of the kidney does not fully develop in the womb. Numerous genes have been identified that when mutated, result in renal dysplasia. This has encouraged the authors to search for additional genes and variants potentially linked to renal anomalies. Using next‑generation sequencing combined with Sanger sequencing, a missense variant in the ITGA8 gene (NM_003638.2:c.1961C>T; p.Ser654Leu) associated with renal hypodysplasia was identified. Detailed studies on this variant revealed that Ser654 is conserved across species, and the mutation is located in the extracellular domain of the protein, which plays an essential role in ligand binding and protein‑protein interactions. This is the first study presenting the clinical correlation of the ITGA8 variant (Ser654Leu) with renal hypodysplasia.

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1	Capone VP, Morello W, Taroni F and Montini G: Genetics of congenital anomalies of the kidney and urinary tract: The current state of play. Int J Mol Sci. 18(796)2017.PubMed/NCBI View Article : Google Scholar
2	Xue C and Mei CL: Polycystic KIDNEY DISEASE AND RENAL FIBROSis. Adv Exp Med Biol. 1165:81–100. 2019.PubMed/NCBI View Article : Google Scholar
3	Pichler R, Oswald J, Glodny B, Skradski V, Aigner F and Rehder P: Unilateral renal agenesis with absent ductus deferens, epididymis and seminal vesicle: Incidental finding in a 22-year-old patient with maldevelopment of the mesonephric duct. Urol Int. 86:365–369. 2011.PubMed/NCBI View Article : Google Scholar
4	Huber C, Shazly SA, Blumenfeld YJ, Jelin E and Ruano R: Update on the prenatal diagnosis and outcomes of fetal bilateral renal agenesis. Obstet Gynecol Surv. 74:298–302. 2019.PubMed/NCBI View Article : Google Scholar
5	Gómez-Conde S, Dunand O, Hummel A, Morinière V, Gauthier M, Mesnard L and Heidet L: Bi-allelic pathogenic variants in ITGA8 cause slowly progressive renal disease of unknown etiology. Clin Genet. 103:114–118. 2023.PubMed/NCBI View Article : Google Scholar
6	Schmidt W, Schroeder TM, Buchinger G and Kubli F: Genetics, pathoanatomy and prenatal diagnosis of Potter I syndrome and other urogenital tract diseases. Clin Genet. 22:105–127. 1982.PubMed/NCBI View Article : Google Scholar
7	Cain DR, Griggs D, Lackey DA and Kagan BM: Familial renal agenesis and total dysplasia. Am J Dis Child. 128:377–380. 1974.PubMed/NCBI View Article : Google Scholar
8	Pashayan HM, Dowd T and Nigro AV: Bilateral absence of the kidneys and ureters. Three cases reported in one family. J Med Genet. 14:205–209. 1977.PubMed/NCBI View Article : Google Scholar
9	Sanna-Cherchi S, Caridi G, Weng PL, Scolari F, Perfumo F, Gharavi AG and Ghiggeri GM: Genetic approaches to human renal agenesis/hypoplasia and dysplasia. Pediatr Nephrol. 22:1675–1684. 2007.PubMed/NCBI View Article : Google Scholar
10	Weber S, Moriniere V, Knüppel T, Charbit M, Dusek J, Ghiggeri GM, Jankauskiené A, Mir S, Montini G, Peco-Antic A, et al: Prevalence of mutations in renal developmental genes in children with renal hypodysplasia: Results of the ESCAPE study. J Am Soc Nephrol. 17:2864–2870. 2006.PubMed/NCBI View Article : Google Scholar
11	Humbert C, Silbermann F, Morar B, Parisot M, Zarhrate M, Masson C, Tores F, Blanchet P, Perez MJ, Petrov Y, et al: Integrin alpha 8 recessive mutations are responsible for bilateral renal agenesis in humans. Am J Hum Genet. 94:288–294. 2014.PubMed/NCBI View Article : Google Scholar
12	Fitzsimmons ED and Bajaj T: Embryology, amniotic fluid. StatPearls Publishing, pp1-4, 2019.
13	Zilberman Sharon N, Pekar-Zlotin M, Kugler N, Accart Z, Nimrodi M, Melcer Y, Cuckle H and Maymon R: Oligohydramnios: How severe is severe? J Matern Fetal Neonatal Med. 35:5754–5760. 2022.PubMed/NCBI View Article : Google Scholar
14	Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, et al: Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology. Genet Med. 17:405–424. 2015.PubMed/NCBI View Article : Google Scholar
15	Kim DE, Chivian D and Baker D: Protein structure prediction and analysis using the Robetta server. Nucleic Acids Res. 32:W526–W531. 2004.PubMed/NCBI View Article : Google Scholar
16	Rodrigues CHM, Pires DEV and Ascher DB: DynaMut: Predicting the impact of mutations on protein conformation, flexibility and stability. Nucleic Acids Res. 46:W350–W355. 2018.PubMed/NCBI View Article : Google Scholar
17	Pandurangan AP, Ochoa-Montaño B, Ascher DB and Blundell TL: SDM: A server for predicting effects of mutations on protein stability. Nucleic Acids Res. 45:W229–W235. 2017.PubMed/NCBI View Article : Google Scholar
18	Frappier V, Chartier M and Najmanovich RJ: ENCoM server: Exploring protein conformational space and the effect of mutations on protein function and stability. Nucleic Acids Res. 43:W395–W400. 2015.PubMed/NCBI View Article : Google Scholar
19	Delano WL: The PyMOL molecular graphics system. CCP4 Newsletter on protein crystallography. Computer Science, Chemistry, 2002.
20	Springer TA: Folding of the N-terminal, ligand-binding region of integrin alpha-subunits into a beta-propeller domain. Proc Natl Acad Sci USA. 94:65–72. 1997.PubMed/NCBI View Article : Google Scholar
21	Loftus JC, Smith JW and Ginsberg MH: Integrin-mediated cell adhesion: The extracellular face. J Biol Chem. 269:25235–25238. 1994.PubMed/NCBI
22	Pavlović N, Kelam N, Racetin A, Filipović N, Pogorelić Z, Prusac IK and Vukojević K: Expression profiles of ITGA8 and VANGL2 Are altered in congenital anomalies of the kidney and urinary tract (CAKUT). Molecules. 29(3294)2024.PubMed/NCBI View Article : Google Scholar
23	Marek I, Hilgers KF, Rascher W, Woelfle J and Hartner A: A role for the alpha-8 integrin chain (itga8) in glomerular homeostasis of the kidney. Mol Cell Pediatr. 7(13)2020.PubMed/NCBI View Article : Google Scholar