Fabry disease (FD) is an X-linked inborn error of glycosphingolipid catabolism that results from mutations in the alpha-galactosidase A (GLA) gene. Evaluating the enzymatic activity in male individuals usually performs the diagnosis of the disease, but in female carriers the diagnosis based only on enzyme assays is often inconclusive. in this work, we analyzed 568 individuals from 102 families with suspect of FD. Overall, 51 families presented 38 alterations in the GLA gene, among which 19 were not previously reported in literature. the alterations included 17 missense mutations, 7 nonsense mutations, 7 deletions, 6 insertions and 1 in the splice site. Six alterations (R112C, R118C, R220X, R227X, R342Q and R356W) occurred at CpG dinucleotides. Five mutations not previously described in the literature (A156D, K237X, A292V, I317S, c.1177_1178insG) were correlated with low GLA enzyme activity and with prediction of molecular damages. From the 13 deletions and insertions, 7 occurred in exons 6 or 7 (54%) and 11 led to the formation of a stop codon. the present study highlights the detection of new genomic alterations in the GLA gene in the Brazilian population, facilitating the selection of patients for recombinant enzyme-replacement trials and offering the possibility to perform prenatal diagnosis. Journal of Human Genetics (2012) 57, 347-351; doi:10.1038/jhg.2012.32; published online 3 May 2012
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机译：法布里病（FD）是糖鞘脂分解代谢的X连锁先天性错误，是由α-半乳糖苷酶A（GLA）基因突变引起的。通常在男性中评估酶活性可以诊断出该疾病，但是在女性携带者中，仅基于酶分析的诊断通常是不确定的。在这项工作中，我们分析了来自102个家庭的FD嫌疑人的568个人。总的来说，有51个家庭的GLA基因发生了38个改变，其中19个以前没有文献报道。这些改变包括17个错义突变，7个无义突变，7个缺失，6个插入和1个剪接位点。在CpG二核苷酸处发生了六个改变（R112C，R118C，R220X，R227X，R342Q和R356W）。先前文献中未描述的五个突变（A156D，K237X，A292V，I317S，c.1177_1178insG）与低GLA酶活性和分子损伤的预测相关。从13个缺失和插入中，有7个出现在第6或7个外显子中（占54％），第11个导致终止密码子的形成。本研究着重介绍了在巴西人群中检测到GLA基因新的基因组改变，为重组酶置换试验的患者选择提供了便利，并提供了进行产前诊断的可能性。 Journal of Human Genetics（2012）57，347-351; doi：10.1038 / jhg.2012.32;在线发布于2012年5月3日
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