Encephalophaty Caused by Novel Mutation in the CMP-Sialic Acid Transporter, SLC35A1

BOBBY G. NG; CARLA G. ASTEGGIANO; MARTIN KIRCHER; KATI J. BUCKINGHAM; KIMIYO RAYMOND; DEBORAH A. NICKERSON; JAY SHENDURE; MICHEL J. BAMSHAD; MATTHIAS ENSSLEN; HUDSON H. FREEZE

American journal of Medical Genetics: Part A

Wiley

Año: 2017

1552-4833

Transport of activated nucleotic-sugars into the Golgi is critical for proper glycosylation and mutation in this 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 Glu196Lys, in the CMP-sialic acid transporter, SLC35A1.Patient primary fibroblast 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 Golgishowed a substantial decrease in overall rate of transport. Here we characterize only the third reported individual with mutations in SLC35A1, who presented with severe neurological phenotype, but without hematological abnormalities.