Centro de Investigación Social Avanzada, Querétaro, Mexico; Cardiovascular Research Center, Mount Sinai School of Medicine, New York, New York; Universidad Panamericana, México, D.F., Mexico.
Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran, México, D.F., Mexico.
Arch Med Res. 2014 Apr;45(3):257-62. doi: 10.1016/j.arcmed.2014.03.005. Epub 2014 Mar 20.
Fabry's disease (FD) is an X-linked lysosomal disorder caused by a deficiency of the enzyme α-galactosidase A that produces accumulation of glycosphingolipids with clinical abnormalities of skin, eye, kidney, heart, brain, and peripheral nervous system. We undertook this study to describe the molecular characteristics of the first four Mexican patients with diagnosis of FD with significant renal involvement, correlating these molecular characteristics with clinical, pathological and biochemical findings.
Genomic DNA from Mexican nonrelated patients with presumptive diagnosis of FD was sequenced by polymerase chain reaction (PCR). DNA sequences were compared against sequences in world data bank gene for alpha-galactosidase A (α-GLA, ENSG00000102393) using the BLAST database.
Three patients were confirmed as having FD by displaying mutations in the α-GLA gene. The mutations found are a substitution (p.L243 F) in patient 1, and a substitution (p.A156 V) in patient 3. These two mutations had been previously reported. The new mutation was in patient 2 who displayed a deletion (c.260delA) changing the open reading frame from codon 86 and a stop codon at the 105th residue of the protein, (instead of 429 AA). The fourth patient had lack of mutations in any of the seven exons of α-GLA or 25 base-pair flanking regions; had mild manifestations with kidney histopathological diagnosis of FD that gave us a final diagnosis of atypical phenotype of FD.
Although the sample is small, it gives a first idea of the molecular and clinical heterogeneity of FD in a Mexican population.
法布里病（FD）是一种 X 连锁溶酶体贮积病，由α-半乳糖苷酶 A 缺乏引起，导致糖脂在皮肤、眼睛、肾脏、心脏、大脑和周围神经系统中积累，出现临床异常。我们进行这项研究是为了描述前四个具有明显肾脏受累的墨西哥 FD 诊断患者的分子特征，将这些分子特征与临床、病理和生化发现相关联。
使用聚合酶链反应（PCR）对有 FD 疑似诊断的墨西哥非相关患者的基因组 DNA 进行测序。使用 BLAST 数据库将 DNA 序列与世界基因数据库中α-半乳糖苷酶 A（α-GLA，ENSG00000102393）的序列进行比较。
三个患者通过在 α-GLA 基因中发现突变被确认为 FD。发现的突变是患者 1 中的替换（p.L243 F）和患者 3 中的替换（p.A156 V）。这两个突变之前已有报道。新的突变发生在患者 2 中，显示出缺失（c.260delA），导致从密码子 86 开始的开放阅读框改变，并在蛋白质的第 105 位产生终止密码子（而不是 429 个 AA）。第四个患者在 α-GLA 的任何七个外显子或 25 个碱基对侧翼区域均未发现突变；有轻度临床表现，肾脏组织病理学诊断为 FD，最终诊断为 FD 的非典型表型。
尽管样本量较小，但它为墨西哥人群中 FD 的分子和临床异质性提供了初步的认识。
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