Ng Bobby G, Asteggiano Carla G, Kircher Martin, Buckingham Kati J, Raymond Kimiyo, Nickerson Deborah A, Shendure Jay, Bamshad Michael J, Ensslen Matthias, Freeze Hudson H
Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
CONICET - Centro de Estudio de las Metabolopatías Congénitas, Universidad Nacional de Córdoba, Facultad de Medicina, Universidad Católica de Córdoba, Córdoba, Argentina.
Am J Med Genet A. 2017 Nov;173(11):2906-2911. doi: 10.1002/ajmg.a.38412. Epub 2017 Aug 29.
Transport of activated nucleotide-sugars into the Golgi is critical for proper glycosylation and mutations in these transporters cause a group of rare genetic disorders termed congenital disorders of glycosylation. We performed exome sequencing on an individual with a profound neurological presentation and identified rare compound heterozygous mutations, p.Thr156Arg and p.Glu196Lys, in the CMP-sialic acid transporter, SLC35A1. Patient primary fibroblasts and serum showed a considerable decrease in the amount of N- and O-glycans terminating in sialic acid. Direct measurement of CMP-sialic acid transport into the Golgi showed a substantial decrease in overall rate of transport. Here we report the identification of the third patient with CMP-sialic acid transporter deficiency, who presented with severe neurological phenotype, but without hematological abnormalities.
活化的核苷酸糖转运至高尔基体对于正确的糖基化至关重要，这些转运体的突变会导致一组罕见的遗传性疾病，称为先天性糖基化障碍。我们对一名有严重神经学表现的个体进行了外显子组测序，在CMP-唾液酸转运体SLC35A1中鉴定出罕见的复合杂合突变p.Thr156Arg和p.Glu196Lys。患者原代成纤维细胞和血清中，以唾液酸为末端的N-聚糖和O-聚糖数量显著减少。对CMP-唾液酸转运至高尔基体的直接测量显示，整体转运速率大幅下降。在此我们报告了第三例CMP-唾液酸转运体缺乏症患者，该患者表现出严重的神经学表型，但无血液学异常。
