Al-Obaide Mohammed A, Al-Obaidi Ibtisam I, Vasylyeva Tetyana L
Department of Pediatrics, School of Medicine, Texas Tech University Health Sciences Center, Amarillo, TX 79106, USA.
Biomed Rep. 2022 Jun 24;17(2):71. doi: 10.3892/br.2022.1554. eCollection 2022 Aug.
Fabry disease (FD) is a rare inherited disease characterized by a wide range of symptoms attributed to mutations resulting in defective α-galactosidase A (α-Gal A) and accumulation of glycosphingolipids. The locus is paired in a divergent manner with the heterogeneous nuclear ribonucleoprotein locus mapped in the readthrough locus. As a follow-up to our recent finding of the co-regulation of and via a bidirectional promoter (BDP) in normal kidney and skin cells, the potential accumulative influence of BDP methylation and mutation on the severity of FD in patients from the same family, two males and two females carrying a 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 was significantly low (P<0.05), and showed a tendency of low expression (P=0.1) when BDP methylation was elevated in FD patients, compared with low BDP methylation and high expression (P<0.05), and a high trend of 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 - BDP may serve a role in diagnosing and treating FD.
法布里病（FD）是一种罕见的遗传性疾病，其特征是由于突变导致α-半乳糖苷酶A（α-Gal A）缺陷和糖鞘脂积累而出现多种症状。该基因座与定位在通读基因座中的异质核糖核蛋白基因座以不同方式配对。作为我们最近在正常肾细胞和皮肤细胞中发现通过双向启动子（BDP）对[基因名称1]和[基因名称2]进行共同调控的后续研究，本研究探讨了BDP甲基化和[基因突变名称]对来自同一家庭的两名男性和两名女性携带c.1033_1034delTC（p.Ser345Argfs）缺失突变的FD患者病情严重程度的潜在累积影响。与对照组相比，对FD患者的分子分析显示，当FD患者中BDP甲基化升高时，[基因名称1]的表达显著降低（P<0.05），而[基因名称2]表现出低表达趋势（P = 0.1），与之相比，BDP甲基化低且[基因名称2]表达高（P<0.05），且在正常个体中[基因名称2]表达呈高趋势。在三名患者中观察到了该突变和BDP甲基化对疾病严重程度的累积影响。一名男性FD患者，是该FD家族的成员，被诊断为肾功能进行性丧失、高血压，最终中风，其α-Gal A酶活性水平最低，显示出最高的BDP DNA甲基化水平。结论是，[基因名称1]-BDP的DNA甲基化可能在FD的诊断和治疗中发挥作用。
