Transcriptomic Analysis of GLUT10 Deficiency in Arterial Tortuosity Syndrome
References
- Coucke PJ, Willaert A, Wessels MW, Callewaert B, Zoppi N, De Backer J, Fox JE, Mancini GM, Kambouris M, Gardella R, Facchetti F, Willems PJ, Forsyth R, Dietz HC, Barlati S, Colombi M, Loeys B, De Paepe A. Mutations in the facilitative glucose transporter GLUT10 alter angio-genesis and cause arterial tortuosity syndrome, Nat Genet. 2006;38(4):452–457.
- Ertugrul A. Diffuse tortuosity and lengthening of the arteries. Circulation. 1967;36(3):400-407.
- Pletcher BA, Fox JE, Boxer RA, Singh S, Blumenthal D, Cohen T, Brunson S, Tafreshi P, & Kahn E. Four sibs with arterial tortuosity: Description and review of the literature. Am J Med Genet. 1996;66(2):121–128.
- Wessels MW, Catsman-Berrevoets CE, Mancini GM, Breuning MH, Hoogeboom JJ, Stroink H, Frohn-Mulder I, Coucke PJ, Paepe AD, Niermeijer MF, & Willems PJ. Three new families with arterial tortuosity syndrome. Am J Med Genet. 2004;131(2):134–43.
- Hardin JS, Zarate YA, Callewaert B, Phillips PH, Warner DB. Ophthalmic findings in patients with arterial tortuosity syndrome and carriers: A case series. Ophthalmic Genet. 2018;39(1):29–34.
- Hasler S, Stürmer J, Kaufmann C. Keratoglobus and deep stromal corneal opacification in a case of arterial tortuosity syndrome. Klin Monbl Augenheilkd. 2011;228(4):345–346.
- Beyens A, Albuisson J, Boel A, Al-Essa M, Al-Manea W, Bonnet D, Bostan O, Boute O, et al. Arterial tortuosity syndrome: 40 new families and literature review. Genetics in Medicine. 2018;20(10):1236–45.
- Albuisson J, Moceri P, Flori E, Belli E, Gronier C, Jeunemaitre X. Clinical utility gene card for: Arterial tortuosity syndrome. European Journal of Human Genetics. 2015;23:8–10.
- Callewaert BL, Willaert A, Kerstjens-Frederikse WS, De Backer J, Devriendt K. et al. Arterial Tortuosity Syndrome: Clinical and Molecular Findings in 12 Newly Identified Families. Hum Mutation. 2008;29(1):150–8.
- Joost Hans-Georg TB. The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members. Mol Membr Biol. 2001;18(4):247–256.
- Long W, Cheeseman CI. Structure of, and functional insight into the GLUT family of membrane transporters. Cell Health Cytoskelet. 2015;7:167–183.
- Dawson PA, Mychaleckyj JC, Fossey SC, Mihic SJ, Crad-dock AL, Bowden DW. Sequence and Functional Analysis of GLUT10: A glucose transporter in the type 2 diabetes-linked region of chromosome 20q12-13.1. Mol Genet Metab. 2001;74:186–99.
- McVie-Wylie AJ, Lamson DR, Chen YT. Molecular cloning of a novel member of the GLUT family of transporters, SLC2A10 (GLUT10), localized on chromosome 20q13.1: A candidate gene for NIDDM susceptibility. Genomics. 2001;72(1):113–7.
- Segade F. Glucose transporter 10 and arterial tortuosity syndrome: The vitamin C connection. FEBS Lett. 2010;584:2990–4.
- Lee YC, Huang HY, Chang CJ, Cheng CH, Chen YT. Mitochondrial GLUT10 facilitates dehydroascorbic acid import and protects cells against oxidative stress: Mechanistic insight into arterial tortuosity syndrome. Hum Mol Genet. 2010;19:3721–33.
- Gamberucci, A, Marcolongo, P, Németh CE, Zoppi N., Szarka, A, et al. GLUT10—lacking in arterial tortuosity syndrome—is localized to the endoplasmic reticulum of human fibroblasts. Int J Mol Sci. 2017;18(8):1820.
- Zoppi N, Chiarelli N, Cinquina V, Ritelli M, Colombi M. GLUT10 deficiency leads to oxidative stress and non-canonical αvβ3 integrin-mediated TGFβ signalling associated with extracellular matrix disarray in arterial tortuosity syndrome skin fibroblasts. Hum Mol Genet. 2015;24:6769–87.
- Loeys BL, Chen J, Neptune ER, Judge DP, Podowski M, et al. A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nature Genetics. 2005;37(3):275–281.
- Wight TN, Merrilees MJ. Proteoglycans in atherosclerosis and restenosis: Key roles for versican. Circ Res. 2004;94(9):1158–67.
- Gardella R, Zoppi N, Assanelli D, Muiesan ML, Barlati S, Colombil M. Exclusion of Candidate Genes in a Family with Arterial Tortuosity Syndrome. Am J Med Genet. 2004;126A(3):221–8.
- Boel, A., Veszelyi, K., Németh, C. E., Beyens, A., Willaert, A., Coucke, P., Callewaert, B., & Margittai, É. Arterial Tortuosity Syndrome: An Ascorbate Compartmentalization Disorder? Antioxid Redox Signal.2021;34(11):875–89.
- Willaert A, Khatri S, Callewaert BL, Coucke PJ, Crosby SD, Lee JG, Davis EC, Shiva S, Tsang M, De Paepe A, Urban Z. GLUT10 is required for the development of the cardiovascular system and the notochord and connects mitochondrial function to TGFβ signaling. Hum Mol Genet. 2011;21(6):1248–59.
- Callewaert BL, Loeys BL, Casteleyn C, Willaert A, Dewint P, De Backer J, Sedlmeier R, Simoens P, De Paepe AM, & Coucke PJ. Absence of arterial phenotype in mice with homozygous slc2A10 Missense substitutions. Genesis. 2008;46:385–9.
- Boel, A., Burger, J., Vanhomwegen, M., Beyens, A., Renard, M., Barnhoorn, S., Casteleyn, C., Reinhardt, D. P., Descamps, B., Vanhove, C., van der Pluijm, I., Coucke, P., Willaert, A., Essers, J., & Callewaert, B. Slc2a10 knockout mice deficient in ascorbic acid synthesis recapitulate aspects of arterial tortuosity syndrome and display mitochondrial respiration defects. Hum Mol Genet. 2020;29(9):1476–1488.
- Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gasti-er-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., Voelkerding, K., Rehm, H. L., & ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: A joint consen-sus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine. 2015;17(5):405–424.
- Kim, A. H., Sakin, I., Viviano, S., Tuncel, G., Aguilera, S. M., Goles, G., Jeffries, L., Ji, W., Lakhani, S. A., Kose, C. C., Silan, F., Oner, S. S., Kaplan, O. I., MarmaRare Group, Ergoren, M. C., Mishra-Gorur, K., Gunel, M., Sag, S. O., Temel, S. G., & Deniz, E. CC2D1A causes ciliopathy, in-tellectual disability, heterotaxy, renal dysplasia, and abnor-mal CSF flow. Life Sci Alliance. 2024;7:e202402708.
- Vangipuram, M., Ting, D., Kim, S., Diaz, R., & Schüle, B.(2013). Skin punch biopsy explant culture for derivation of primary human fibroblasts. Journal of visualized experi-ments: JoVE, 77, e3779.
- Emisoglu-Kulahli H, Gul S, Morgil H, Ozcan O, Aygenli F, Selvi S, Kavakli IH, Ozturk N. Transcriptome analysis of the circadian clock gene BMAL1 deletion with opposite carcinogenic effects. Funct Integr Genomics. 2021;21(1):1–16.
- Sarayloo E, Tardu M, Unlu YS, Simsek S, Cevahir G, Erkey C, et al. Understanding lipid metabolism in high-lipid-producing Chlorella vulgaris mutants at the genome-wide level. Algal Res. 2017;28:244–52.
- Cavga AD, Tardu M, Korkmaz T, et al. Cryptochrome deletion in p53 mutant mice enhances apoptotic and anti-tumorigenic responses to UV damage at the transcriptome level. Funct Integr Genomics.2019;19:729–42.
- Bolger AM, Lohse M, Usadel B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114–20.
- Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, et al. STAR: Ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29(1):15–21.
- Trapnell C, Roberts A, Goff L, et al. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc. 2012;7(3):562–78.
- Bindea G, Mlecnik B, Hackl H, et al. ClueGO: A Cytos-cape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009;25(8):1091–1093.
- Németh, CE, Nemoda Z, Lőw P, Szabó P, Horváth EZ, Willaert A, Boel A, Callewaert BL, Coucke PJ, Colombi M, Bánhegyi G, & Margittai É. Decreased nuclear ascorbate accumulation accompanied with altered genomic methylation pattern in fibroblasts from arterial tortuosity syndrome patients. Oxid Med Cell Longev. 2019;8156592.
- Morgan MJ, Liu ZG. Crosstalk of reactive oxygen species and NF-κB signaling. Cell Res. 2011;21(1):103–15.
- Morgan MJ, Liu ZG. Reactive oxygen species in TNFα-induced signaling and cell death. Mol Cells. 2010;30(1):1–12.
- Elzi DJ, Song M, Hakala K, Weintraub ST, Shiio Y. Wnt Antagonist SFRP1 Functions as a Secreted Mediator of Senescence. Mol Cell Biol. 2012;32(21):4388–99.
- Dufourcq P, Leroux L, Ezan J, et al. Regulation of endothelial cell cytoskeletal reorganization by a secreted frizzled-related protein-1 and frizzled 4-and frizzled 7-dependent pathway: Role in neovessel formation. American Journal of Pathology. 2008;172(1):37–49.
- Logan CY, Nusse R. The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 2004;20:781–810.
- Ueland T, Otterdal K, Lekva T, Halvorsen B, Gabrielsen A, Sandberg WJ, Paulsson-Berne G., Pedersen TM. et al. Dickkopf-1 enhances inflammatory interaction between platelets and endothelial cells and shows increased expression in atherosclerosis. Arterioscler Thromb Vasc Biol. 2009;29(8):1228–34.
- Sümer C, Boz Er AB, Dinçer T. Keratin 14 is a novel interaction partner of keratinocyte differentiation regulator:receptor-interacting protein kinase 4. Turkish Journal of Biology. 2019;43(4):225–34.
- Dinçer T, Boz Er AB, Er İ, Toraman B, Yildiz G, Kalay E. RIPK4 suppresses the TGF-β1 signaling pathway in Ha-CaT cells. Cell Biol Int. 2020;44(3):848–60.
- Van Loon K, Yemelyanenko-Lyalenko J, Margadant C, Griffioen AW, Huijbers EJM. Role of fibrillin-2 in the control of TGF-β activation in tumor angiogenesis and connective tissue disorders. Biochim Biophys Acta Rev Cancer. 2020;1873(2):188354.
- Cunningham NS, Jenkins NA, Gilbert DJ, Copeland NG, Reddi AH, Lee SJ. Growth/differentiation factor-10: A new member of the transforming growth factor-β superfamily related to bone morphogenetic protein-3. Growth Factors. 1995;12(2):99–109.
- Platko K, Gyulay G, Lebeau PF, MacDonald ME, Lynn EG, Byun JH, Igdoura SA, Holden, RM, et al. GDF10 is a negative regulator of vascular calcification. Journal of Biological Chemistry. 2024;300(11):1–14.
- Hjalt TA, Amendt BA, Murray JC. PITX2 regulates procollagen lysyl hydroxylase (PLOD) gene expression: Implications for the pathology of Rieger syndrome. Journal of Cell Biology. 2001;152(3):545–52.
- Qiu M, Juanito J. Null mutation of Dlx-2 results in abnormal morphogenesis of proximal first and second branchial arch derivatives and abnormal differentiation in the fore-brain. Genes Dev. 1995;9(20):2523–38.
- Kioussi C, Briata P, Baek SH, Rose DW, Hamlet NS, Herman T, Ohgi K, Lin C, et al. Identification of a Wnt/Dvl/β-Catenin → Pitx2 Pathway Mediating Cell-Type-Specific Proliferation during Development cell-type-specific proliferation during development. Cell. 2002;111(5):673–85.
- Grego-Bessa J, Luna-Zurita L, del Monte G, Bolós V, Melgar P, Arandilla A, et al. Notch Signaling Is Essential for Ventricular Chamber Development. Dev Cell. 2007;12(3):415–29.
- Vaiyapuri S, Sage T, Rana RH, Schenk MP, Ali MS, Unsworth AJ, Jones CI, Stainer AR et al. EphB2 regulates contact-dependent and contact-independent signaling to control platelet function. Blood. 2015;125(4):720–31.
DOI: https://doi.org/10.2478/ebtj-2026-0008 | Journal eISSN: 2564-615X
Language: English
Page range: 68 - 80
Published on: Apr 30, 2026
Published by: European Biotechnology Thematic Network Association
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
Related subjects:
© 2026 Gulden Yorgancioglu Budak, Nurdeniz Nalbant, Burcu Turkgenc, Fahrettin Uysal, Ozlem Mehtap Bostan, Sebnem Özemri Sag, Ergun Cil, Sehime G. Temel, published by European Biotechnology Thematic Network Association
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.