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Encephalopathy caused by novel mutations in the CMP‐sialic acid transporter, SLC35A1
Author(s) -
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.
Publication year - 2017
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38412
Subject(s) - sialic acid , glycosylation , transporter , golgi apparatus , phenotype , glycan , exome sequencing , atp binding cassette transporter , mutation , glucose transporter , biochemistry , chemistry , biology , gene , endocrinology , glycoprotein , cell , insulin
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.