Congenital disorders of glycosylation (CDG) comprise a rapidly growing group of inherited disorders in which glycosylation of glycoproteins is defective due to mutations in genes required for the assembly of lipid-linked oligosaccharides, their transfer to nascent glycoproteins (CDG-I) or the processing of protein-bound glycans (CDG-II). Previously' a defect in the GDP-fucose import into the lumen of the Golgi was identified in a person with CDG (A.C.) with a general deficiency of fucosyl residues in glycoproteins. This patient presents the clinical features of leukocyte adhesion deficiency type II (LAD II) including mental retardation, short stature, facial stigmata, and recurrent bacterial peripheral infections with persistently elevated peripheral leukocytes. Using a fucose-specific, lectin-staining procedure for detection of fucosylated glycoproteins and a retroviral cDNA library, we isolated a cDNA complementing the fucosylation defect in the patient's fibroblasts. The cDNA encodes a highly hydrophobic protein of 364 amino acids with multiple putative transmembrane domains. Restoration of GDP-fucose import activity in Golgi-enriched vesicles from the patient's fibroblasts verified the GDP-fucose transporter activity of this protein. We identified two missense mutations in the GDP-fucose transporter cDNA of patient A.C. and of two other people with LAD II. Thus complementation cloning allowed us to identify the human GDP-fucose transporter cDNA and GDP-fucose transporter deficiency as a cause for a new type of CDG. Following the recent recommendations for the nomenclature for CDG, this new type is classified as CDG-IIc (formerly LAD II).

中文翻译：

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互补克隆将CDG-IIc（一种新型的先天性糖基化疾病）识别为GDP-岩藻糖转运蛋白缺陷。

先天性糖基化疾病（CDG）包括一组快速增长的遗传性疾病，其中糖蛋白的糖基化由于组装脂质连接的寡糖，转移至新生糖蛋白（CDG-1）或加工所需的基因突变而有缺陷蛋白结合的聚糖（CDG-II）。以前，在患有CDG（AC）且糖蛋白中岩藻糖基残基普遍缺乏的人中发现了GDP-岩藻糖进入高尔基体腔的缺陷。该患者表现出II型白细胞粘附缺乏症（LAD II）的临床特征，包括智力低下，身材矮小，面部柱头和反复出现的外周细菌性感染，周围性白细胞持续升高。使用特定的岩藻糖，为检测岩藻糖基化糖蛋白和逆转录病毒cDNA文库的凝集素染色程序，我们分离了一个与患者成纤维细胞中岩藻糖基化缺陷互补的cDNA。cDNA编码具有364个氨基酸的高度疏水性蛋白，并带有多个推定的跨膜结构域。从患者的成纤维细胞中富含高尔基体的囊泡中恢复了GDP-岩藻糖的进口活性，证实了该蛋白的GDP-岩藻糖转运蛋白活性。我们在患者AC和另外两名LAD II患者中发现了GDP-岩藻糖转运蛋白cDNA中的两个错义突变。因此，互补克隆使我们能够确定人类GDP-岩藻糖转运蛋白cDNA和GDP-岩藻糖转运蛋白的缺乏是导致新型CDG的原因。根据有关CDG命名法的最新建议，