A new case of UDP-galactose transporter deficiency (SLC35A2-CDG): molecular basis, clinical phenotype, and therapeutic approach
A new case of UDP-galactose transporter deficiency (SLC35A2-CDG): molecular basis, clinical phenotype, and therapeutic approach
复制标题
DOI：
10.1007/s10545-015-9828-6
复制
发表时间：
2015-09-01
影响因子：
4.2
通讯作者：
Marquardt, T.
中科院分区：
文献类型：
--
作者：
Doerre, K.;Olczak, M.;Marquardt, T.
先天性糖基化障碍（CDG）是一组以蛋白质和脂质糖基化异常为特征的遗传性代谢疾病。通常，发生累及中枢神经系统的多系统疾病和多种临床症状。主要特征是发育迟缓、癫痫发作和共济失调。在本文中，我们报告的临床和生化特征的一个5岁的女孩有缺陷的半乳糖基化的N-聚糖，导致发育迟缓，肌肉张力减退，癫痫发作，乳头内陷，视力障碍。下一代测序揭示了X染色体基因SLC 35 A2（溶质载体家族35，UDP-半乳糖转运蛋白，成员A2; MIM 300896）中的从头突变（c.797G > T，p.G266V）。虽然发现该突变是杂合的，但正常等位基因的随机X失活将导致相应细胞中正常SLC 35 A2活性的丧失。通过正常UGT表达构建体（而非突变体）对UGT缺陷型MDCK-RCA（r）和CHO-Lec 8细胞的互补，证明了突变的功能相关性。研究了膳食半乳糖补充对糖基化的影响，显示出转铁蛋白糖基化几乎完全正常化。
Congenital disorders of glycosylation (CDG) are a group of hereditary metabolic diseases characterized by abnormal glycosylation of proteins and lipids. Often, multisystem disorders with central nervous system involvement and a large variety of clinical symptoms occur. The main characteristics are developmental delay, seizures, and ataxia. In this paper we report the clinical and biochemical characteristics of a 5-year-old girl with a defective galactosylation of N-glycans, resulting in developmental delay, muscular hypotonia, epileptic seizures, inverted nipples, and visual impairment. Next generation sequencing revealed a de novo mutation (c.797G > T, p.G266V) in the X-chromosomal gene SLC35A2 (solute carrier family 35, UDP-galactose transporter, member A2; MIM 300896). While this mutation was found heterozygous, random X-inactivation of the normal allele will lead to loss of normal SLC35A2 activity in respective cells. The functional relevance of the mutation was demonstrated by complementation of UGT-deficient MDCK-RCA(r) and CHO-Lec8 cells by normal UGT-expression construct but not by the mutant version. The effect of dietary galactose supplementation on glycosylation was investigated, showing a nearly complete normalization of transferrin glycosylation.