Encephalopathy caused by novel mutations in the CMP-sialic acid transporter, SLC35A1.

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. © 2017 Wiley Periodicals, Inc.

Citation

Bobby G Ng, Carla G Asteggiano, Martin Kircher, Kati J Buckingham, Kimiyo Raymond, Deborah A Nickerson, Jay Shendure, Michael J Bamshad, University of Washington Center for Mendelian Genomics, Matthias Ensslen, Hudson H Freeze. Encephalopathy caused by novel mutations in the CMP-sialic acid transporter, SLC35A1. American journal of medical genetics. Part A. 2017 Nov;173(11):2906-2911

PMID: 28856833

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