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Intellectual disability

Gene: FUT8

Green List (high evidence)

FUT8 (fucosyltransferase 8)
EnsemblGeneIds (GRCh38): ENSG00000033170
EnsemblGeneIds (GRCh37): ENSG00000033170
OMIM: 602589, Gene2Phenotype
FUT8 is in 7 panels

2 reviews

Louise Daugherty (Genomics England Curator)

Comment on list classification: New gene added by external expert and reviewed by curation team, enough evidence to support gene-disease association and relevance to this panel to rate this gene Green
Created: 19 Nov 2018, 1:20 p.m.
Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the intellectual disability panel
Created: 19 Nov 2018, 1:13 p.m.

Konstantinos Varvagiannis (Other)

Green List (high evidence)

PMID: 29304374 reports on 3 unrelated individuals with biallelic pathogenic variants in FUT8.

Two of the patients were born to consanguineous parents and were found to be homozygous for stopgain variants (p.Arg239* in one family and p.Arg315* in the other). A third patient was compound heterozygous for a missense as well as a splice variant.

All three presented with similar phenotype consisting of polyhydramnios (2 out of 3), IUGR and failure to thrive with short stature (3/3), severe developmental delay (3/3) with microcephaly (3/3) and seizures (3/3). Variable respiratory problems were also noted in all.

Western blot demonstrated loss of FUT8 protein expression in one individual homozygous for a stopgain mutation as well as the patient who was compound heterozygous for the missense and the splice variant. The splice variant was further shown to produce a shorter transcript due to lack of exon 9, leading to an in-frame deletion of 59 residues critical for the protein function.

Additional studies confirmed the fucosylation defect compared to controls.

The authors note that while Fut8 knockout mice are born normal, 70% die within the first 3 days due to severe growth retardation and respiratory deficiency (similarly to what is observed in humans, though to a lesser extent).

As a result this gene can be considered for inclusion in this panel probably as green (3 unrelated families, strong additional functional data, consistent phenotype) or amber.
Sources: Literature, Expert Review
Created: 17 Nov 2018, 7:49 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Congenital disorder of glycosylation with defective fucosylation, 618005

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • Congenital disorder of glycosylation with defective fucosylation, 618005
  • Intellectual disability
OMIM
602589
Clinvar variants
Variants in FUT8
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

19 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: fut8 has been classified as Green List (High Evidence).

19 Nov 2018, Gel status: 0

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: FUT8 were changed from Congenital disorder of glycosylation with defective fucosylation, 618005 to Congenital disorder of glycosylation with defective fucosylation, 618005; Intellectual disability

19 Nov 2018, Gel status: 0

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: FUT8 were set to 29304374

17 Nov 2018, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Konstantinos Varvagiannis (Other)

gene: FUT8 was added gene: FUT8 was added to Intellectual disability. Sources: Literature,Expert Review Mode of inheritance for gene: FUT8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FUT8 were set to 29304374 Phenotypes for gene: FUT8 were set to Congenital disorder of glycosylation with defective fucosylation, 618005 Penetrance for gene: FUT8 were set to Complete Review for gene: FUT8 was set to GREEN