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

Ng, Bobby G.; Asteggiano, Carla G.; Kircher, Martin; Buckingham, Kati J.; Raymond, Kimiyo; Nickerson, Deborah A.; Shendure, Jay; Bamshad, Michael J.; Ensslen, Matthias and Freeze, Hudson H. (2017): Encephalopathy caused by novel mutations in the CMP-sialic acid transporter, SLC35A1. In: American Journal of Medical Genetics Part A, Vol. 173, No. 11: pp. 2906-2911

Abstract

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.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1552-4825
• Language: English