Mosaicism of the UDP-Galactose Transporter SLC35A2 Causes a Congenital Disorder of Glycosylation
Mosaicism of the UDP-Galactose Transporter SLC35A2 Causes a Congenital Disorder of Glycosylation
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DOI：
10.1016/j.ajhg.2013.03.012
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发表时间：
2013-04-04
影响因子：
9.8
通讯作者：
Freeze, Hudson H.
中科院分区：
文献类型：
--
作者：
Ng, Bobby G.;Buckingham, Kati J.;Freeze, Hudson H.
生化分析和全外显子组测序鉴定了高尔基体定位的UDP-半乳糖转运蛋白SLC 35 A2的突变，该突变在三个无关家族中定义了一种未诊断的X连锁先天性糖基化障碍（CDG）。每个突变减少UDP-半乳糖转运，导致半乳糖缺乏的糖蛋白。两个受影响的男性体细胞嵌合体，表明野生型SLC 35 A2等位基因可能是生存所必需的。在婴儿期，常用的生物标志物转铁蛋白显示异常糖基化，但其外观在儿童期后期变得正常，没有任何相应的临床改善。这可能表明针对携带突变等位基因的细胞的选择。为了检测其他人与这样的突变，我们建议转铁蛋白测试在婴儿期。在这里，我们报告体细胞嵌合在CDG，我们的工作强调了遗传和生化诊断相结合的重要性。
Biochemical analysis and whole-exome sequencing identified mutations in the Golgi-localized UDP-galactose transporter SLC35A2 that define an undiagnosed X-linked congenital disorder of glycosylation (CDG) in three unrelated families. Each mutation reduced UDP-galactose transport, leading to galactose-deficient glycoproteins. Two affected males were somatic mosaics, suggesting that a wild-type SLC35A2 allele may be required for survival. In infancy, the commonly used biomarker transferrin showed abnormal glycosylation, but its appearance became normal later in childhood, without any corresponding clinical improvement. This may indicate selection against cells carrying the mutant allele. To detect other individuals with such mutations, we suggest transferrin testing in infancy. Here, we report somatic mosaicism in CDG, and our work stresses the importance of combining both genetic and biochemical diagnoses.