Contribution of genotyping in Fabry's disease
Contribution of genotyping in Fabry's disease
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DOI：
10.1016/s0248-8663(10)70027-8
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发表时间：
2010-12-01
影响因子：
0.9
通讯作者：
Maire, I.
中科院分区：
文献类型：
--
作者：
Froissart, R.;Piraud, M.;Maire, I.
法布里病是一种 X 连锁疾病，由编码溶酶体酶 α-半乳糖苷酶 A 的 CIA 基因突变所致。临床上，大多数患者表现为“经典”形式，但已描述了首次或主要累及心脏或肾脏的“变异”形式。杂合子女性最常出现症状，但通常比男性受到的影响要轻。我们对来自 65 个家庭的 170 名患者进行了突变分析，发现了 55 种不同的突变。我们的结果证实了该位点的广泛分子异质性。分子研究可以确认男性患者的诊断以及家庭中杂合女性的可靠诊断，因为生化测试（α-半乳糖苷酶 A 活性和尿 Gb(3) 研究）可以正常。然而，在少数指示病例为女性的病例中，在缺乏广泛的家族研究的情况下，确认（鉴定致病性未知的新错义）或排除（未发现基因改变）杂合子可能仍然很困难。一般来说，基因型/表型相关性仍然很困难，因为只有少数突变更频繁。此外，即使在同一家族内，表型的变异也表明其他因素（遗传和表观遗传）可能影响疾病进展。 (C) 2010 年法国国家医学协会 (SNFMI)。由 Elsevier Masson SAS 出版。版权所有。
Fabry's disease is an X-linked disorder due to mutations in the CIA gene encoding the lysosomal enzyme alpha-galactosidase A. Clinically, most patients present with the "classical" form, though "variant" forms with inaugural or preminent heart or kidney involvement have been described. Heterozygous women are most often symptomatic though generally less severely affected than men.We performed mutation analysis in 170 patients from 65 families and identified 55 different mutations. Our results confirm the wide molecular heterogeneity at this locus. Molecular study allows to confirm the diagnosis in male patients and the reliable diagnosis of heterozygous females in the family as biochemical tests (alpha-galactosidase A activity and urinary Gb(3) study) can be normal. However, in a few cases in which the index case is a female, it may remain difficult in the absence of an extensive familial study, to confirm (identification of a new missense the pathogenicity of which is unknown) or rule out (no gene alteration found) an heterozygote. Generally, genotype/phenotype correlations remain difficult as only a few mutations are more frequent. Furthermore, variations of the phenotype, even within the same family, suggest that other factors (genetic and epigenetic) could influence disease progression. (C) 2010 Societe nationale francaise de medecine interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.