Format

Send to

Choose Destination
Am J Med Genet A. 2017 Nov;173(11):2906-2911. doi: 10.1002/ajmg.a.38412. Epub 2017 Aug 29.

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

Author information

1
Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California.
2
CONICET - Centro de Estudio de las Metabolopatías Congénitas, Universidad Nacional de Córdoba, Facultad de Medicina, Universidad Católica de Córdoba, Córdoba, Argentina.
3
Department of Genome Sciences, University of Washington, Seattle, Washington.
4
Department of Pediatrics, University of Washington, Seattle, Washington.
5
Biochemical Genetics Laboratory, Mayo Clinic College of Medicine, Rochester, Minnesota.
6
Howard Hughes Medical Institute, University of Washington, Seattle, Washington.
7
Department of Paediatric Neurology and Developmental Medicine, Hauner Children's Hospital, University of Munich Lindwurmstrasse 4, Munich, Germany.

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.

KEYWORDS:

SLC35A1; congenital disorders of glycosylation; golgi; nucleotide-sugar transporter; seizures; sialic acid

PMID:
28856833
PMCID:
PMC5650519
[Available on 2018-11-01]
DOI:
10.1002/ajmg.a.38412
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center