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Article Open Access

The potential consequences of bidirectional promoter methylation on GLA and HNRNPH2 expression in Fabry disease phenotypes in a family of patients carrying a GLA deletion variant

  • Authors:
    • Mohammed A. Al-Obaide
    • Ibtisam I. Al-Obaidi
    • Tetyana L. Vasylyeva
  • View Affiliations / Copyright

    Affiliations: Department of Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA
    Copyright: © Al-Obaide et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 71
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    Published online on: June 24, 2022
       https://doi.org/10.3892/br.2022.1554
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Abstract

Fabry disease (FD) is a rare inherited disease characterized by a wide range of symptoms attributed to GLA mutations resulting in defective α‑galactosidase A (α‑Gal A) and accumulation of glycosphingolipids. The GLA locus is paired in a divergent manner with the heterogeneous nuclear ribonucleoprotein HNRNPH2 locus mapped in the RPL36A‑HNRNPH2 readthrough locus. As a follow‑up to our recent finding of the co‑regulation of GLA and HNRNPH2 via a bidirectional promoter (BDP) in normal kidney and skin cells, the potential accumulative influence of BDP methylation and GLA mutation on the severity of FD in patients from the same family, two males and two females carrying a GLA deletion mutation, c.1033_1034delTC (p.Ser345Argfs) was addressed in the present study. The molecular analyses of the FD patients compared with the control revealed that the expression of GLA was significantly low (P<0.05), and HNRNPH2 showed a tendency of low expression (P=0.1) when BDP methylation was elevated in FD patients, compared with low BDP methylation and high GLA expression (P<0.05), and a high trend of HNRNPH2 expression in normal individuals. The accumulative effects of the mutation and BDP methylation with the severity of the disease were observed in three patients. One male FD patient, a member of the FD family diagnosed with progressive loss of kidney function, hypertension, and eventually a stroke, and the lowest level of α‑Gal A enzyme activity showed the highest BDP DNA methylation level. It is concluded that the DNA methylation of GLA‑HNRNPH2 BDP may serve a role in diagnosing and treating FD.
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Copy and paste a formatted citation
Spandidos Publications style
Al-Obaide MA, Al-Obaidi II and Vasylyeva TL: The potential consequences of bidirectional promoter methylation on <em>GLA and</em> <em>HNRNPH2</em> expression in Fabry disease phenotypes in a family of patients carrying a <em>GLA</em> deletion variant. Biomed Rep 17: 71, 2022.
APA
Al-Obaide, M.A., Al-Obaidi, I.I., & Vasylyeva, T.L. (2022). The potential consequences of bidirectional promoter methylation on <em>GLA and</em> <em>HNRNPH2</em> expression in Fabry disease phenotypes in a family of patients carrying a <em>GLA</em> deletion variant. Biomedical Reports, 17, 71. https://doi.org/10.3892/br.2022.1554
MLA
Al-Obaide, M. A., Al-Obaidi, I. I., Vasylyeva, T. L."The potential consequences of bidirectional promoter methylation on <em>GLA and</em> <em>HNRNPH2</em> expression in Fabry disease phenotypes in a family of patients carrying a <em>GLA</em> deletion variant". Biomedical Reports 17.2 (2022): 71.
Chicago
Al-Obaide, M. A., Al-Obaidi, I. I., Vasylyeva, T. L."The potential consequences of bidirectional promoter methylation on <em>GLA and</em> <em>HNRNPH2</em> expression in Fabry disease phenotypes in a family of patients carrying a <em>GLA</em> deletion variant". Biomedical Reports 17, no. 2 (2022): 71. https://doi.org/10.3892/br.2022.1554
Copy and paste a formatted citation
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Spandidos Publications style
Al-Obaide MA, Al-Obaidi II and Vasylyeva TL: The potential consequences of bidirectional promoter methylation on <em>GLA and</em> <em>HNRNPH2</em> expression in Fabry disease phenotypes in a family of patients carrying a <em>GLA</em> deletion variant. Biomed Rep 17: 71, 2022.
APA
Al-Obaide, M.A., Al-Obaidi, I.I., & Vasylyeva, T.L. (2022). The potential consequences of bidirectional promoter methylation on <em>GLA and</em> <em>HNRNPH2</em> expression in Fabry disease phenotypes in a family of patients carrying a <em>GLA</em> deletion variant. Biomedical Reports, 17, 71. https://doi.org/10.3892/br.2022.1554
MLA
Al-Obaide, M. A., Al-Obaidi, I. I., Vasylyeva, T. L."The potential consequences of bidirectional promoter methylation on <em>GLA and</em> <em>HNRNPH2</em> expression in Fabry disease phenotypes in a family of patients carrying a <em>GLA</em> deletion variant". Biomedical Reports 17.2 (2022): 71.
Chicago
Al-Obaide, M. A., Al-Obaidi, I. I., Vasylyeva, T. L."The potential consequences of bidirectional promoter methylation on <em>GLA and</em> <em>HNRNPH2</em> expression in Fabry disease phenotypes in a family of patients carrying a <em>GLA</em> deletion variant". Biomedical Reports 17, no. 2 (2022): 71. https://doi.org/10.3892/br.2022.1554
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