Unknown

Dataset Information

0

Pathogenic Variants in Fucokinase Cause a Congenital Disorder of Glycosylation.

ABSTRACT: FUK encodes fucokinase, the only enzyme capable of converting L-fucose to fucose-1-phosphate, which will ultimately be used for synthesizing GDP-fucose, the donor substrate for all fucosyltransferases. Although it is essential for fucose salvage, this pathway is thought to make only a minor contribution to the total amount of GDP-fucose. A second pathway, the major de novo pathway, involves conversion of GDP-mannose to GDP-fucose. Here we describe two unrelated individuals who have pathogenic variants in FUK and who presented with severe developmental delays, encephalopathy, intractable seizures, and hypotonia. The first individual was compound heterozygous for c.667T>C (p.Ser223Pro) and c.2047C>T (p.Arg683Cys), and the second individual was homozygous for c.2980A>C (p.Lys994Gln). Skin fibroblasts from the first individual confirmed the variants as loss of function and showed significant decreases in total GDP-[3H] fucose and [3H] fucose-1-phosphate. There was also a decrease in the incorporation of [5,6-3H]-fucose into fucosylated glycoproteins. Lys994 has previously been shown to be an important site for ubiquitin conjugation. Here, we show that loss-of-function variants in FUK cause a congenital glycosylation disorder characterized by a defective fucose-salvage pathway.

SUBMITTER: Ng BG 

PROVIDER: S-EPMC6288200 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Pathogenic Variants in Fucokinase Cause a Congenital Disorder of Glycosylation.

Ng Bobby G BG   Rosenfeld Jill A JA   Emrick Lisa L   Jain Mahim M   Burrage Lindsay C LC   Lee Brendan B   Craigen William J WJ   Bearden David R DR   Graham Brett H BH   Freeze Hudson H HH  

American journal of human genetics 20181129 6

FUK encodes fucokinase, the only enzyme capable of converting L-fucose to fucose-1-phosphate, which will ultimately be used for synthesizing GDP-fucose, the donor substrate for all fucosyltransferases. Although it is essential for fucose salvage, this pathway is thought to make only a minor contribution to the total amount of GDP-fucose. A second pathway, the major de novo pathway, involves conversion of GDP-mannose to GDP-fucose. Here we describe two unrelated individuals who have pathogenic va  ...[more]

Similar Datasets

Unknown Bi-allelic variants in the ER quality-control mannosidase gene EDEM3 cause a congenital disorder of glycosylation.
| S-EPMC8322938 | biostudies-literature
Unknown A rare cause of infantile achalasia: GMPPA-congenital disorder of glycosylation with two novel compound heterozygous variants.
| S-EPMC9283290 | biostudies-literature
Unknown Active site variants in STT3A cause a dominant type I congenital disorder of glycosylation with neuromusculoskeletal findings.
| S-EPMC8595932 | biostudies-literature
Unknown KIF21A pathogenic variants cause congenital fibrosis of extraocular muscles type 3.
| S-EPMC7987873 | biostudies-literature
Unknown Biallelic Mutations in FUT8 Cause a Congenital Disorder of Glycosylation with Defective Fucosylation.
| S-EPMC5777984 | biostudies-literature
Unknown PGM3 mutations cause a congenital disorder of glycosylation with severe immunodeficiency and skeletal dysplasia.
| S-EPMC4085583 | biostudies-literature
Unknown Mutations in the translocon-associated protein complex subunit SSR3 cause a novel congenital disorder of glycosylation.
| S-EPMC6739144 | biostudies-literature
Unknown Pathogenic variants in TNNC2 cause congenital myopathy due to an impaired force response to calcium.
| S-EPMC8087209 | biostudies-literature
Unknown Pathogenic variants in COL6A3 cause Ullrich-like congenital muscular dystrophy in young Labrador Retriever dogs.
| S-EPMC7292757 | biostudies-literature
Unknown TMEM165 deficiency causes a congenital disorder of glycosylation.
| S-EPMC3397274 | biostudies-literature