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Genetic epilepsy syndromes

Gene: FUK

Amber List (moderate evidence)

FUK (fucokinase)
EnsemblGeneIds (GRCh38): ENSG00000157353
EnsemblGeneIds (GRCh37): ENSG00000157353
OMIM: 608675, Gene2Phenotype
FUK is in 4 panels

5 reviews

Rebecca Foulger (Genomics England curator)

I don't know

Kept rating as Amber based on Amber post-Webex review from Helen Lord.
Created: 9 Sep 2019, 10:21 a.m. | Last Modified: 9 Sep 2019, 10:21 a.m.
Panel Version: 1.314
Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.
Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.
Panel Version: 1.262

Helen Lord (Oxford Medical Genetics Laboratories)

I don't know

AR CDGF2. Ng et al, 2018 (30503518) - 2 unrelated children aged 6 and 7 with a severe multisystem disorder apparent from early infancy. Both developed intractable seizures with epileptic encephalopathy. Hom/compound het missense variants detected. Immunoblot analysis of cells from patient 1 showed a 60-80% reduction in FUK levels and severely decreased FUK activity compared to controls - consistent with LOF. no cell lines available for patient 2.
Created: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.
Panel Version: 1.261

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Catherine Snow (Genomics England)

FCSK/FUK was added to the Genetic epilepsy syndromes panel and rated Amber by Konstantinos Varvagiannis. Ng et al. (PMID: 30503518) reported on 2 unrelated individuals with biallelic pathogenic variants in FUK. FUK has been added to OMIM and DDG2P based on this publications. No details were given at the age of onset of epilepsy. As there are no further cases or animal models to support these variants in the literature, inline with current guidelines, gene will remain Amber.
Created: 25 Jun 2019, 1:16 p.m. | Last Modified: 25 Jun 2019, 1:16 p.m.
Panel Version: 0.13

Louise Daugherty (Genomics England Curator)

Added new-gene-name tag, new approved HGNC gene symbol for FUK is FCSK
Created: 1 Mar 2019, 4:11 p.m.

Konstantinos Varvagiannis (Other)

I don't know

Ng et al. (PMID: 30503518) report on 2 unrelated individuals with biallelic pathogenic variants in FUK. The common features consisted of feeding difficulties, hypotonia, global developmental delay with severe intellectual disability, seizures as well as visual impairment.

The first patient was compound heterozygous for 2 missense variants (Ser223Pro and Arg683Cys) while the second - born to consanguineous parents - was homozygous for Lys994Gln.

Significant reduction in the FUK protein amount was demonstrated upon Western blot for the first individual for whom fibroblast and lymphoblast cell lines were available.

Fucokinase (FUK) is an enzyme of the fucose salvage pathway, one of the mechanisms (the other and main contributor being the de novo pathway) for synthesis of GDP-fucose. GDP-fucose is a donor substrate for fucosylation, a form of glycosylation. Significant decrease of fucokinase activity was shown for this individual when compared to controls.

Cell lines from the second individual were not available for expression/functional studies.

Overall the authors suggest that loss-of-function variants cause a congenital disorder of glycosylation with ID and seizures.

There are no further cases published in the literature.

FUK is not associated with any phenotype in OMIM nor in G2P.

As a result this gene can be considered for inclusion in this panel as amber.

[You might consider inclusion of this gene also in the CDG gene panel].
Sources: Literature
Created: 13 Dec 2018, 7:38 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Feeding difficulties; Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures; Abnormality of vision

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Expert Review
  • Expert Review Amber
  • Expert Review
Phenotypes
  • Seizures
  • Generalized hypotonia
  • Feeding difficulties
  • Intellectual disability
  • Global developmental delay
  • Abnormality of vision
  • Congenital disorder of glycosylation with defective fucosylation 2, 618324
Tags
new-gene-name
OMIM
608675
Clinvar variants
Variants in FUK
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

17 Sep 2019, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to FUK.

17 Sep 2019, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to FUK.

22 Jul 2019, Gel status: 2

Added New Source, Added New Source, Set Phenotypes, Status Update

Catherine Snow (Genomics England)

Source Expert Review was added to FUK. Source Expert Review Amber was added to FUK. Added phenotypes Congenital disorder of glycosylation with defective fucosylation 2, 618324 for gene: FUK Rating Changed from No List (delete) to Amber List (moderate evidence)

1 Mar 2019, Gel status: 0

Added Tag

Louise Daugherty (Genomics England Curator)

Tag new-gene-name tag was added to gene: FUK.

13 Dec 2018, Gel status: 0

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

Konstantinos Varvagiannis (Other)

gene: FUK was added gene: FUK was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: FUK was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FUK were set to 30503518 Phenotypes for gene: FUK were set to Feeding difficulties; Generalized hypotonia; Global developmental delay; Intellectual disability; Seizures; Abnormality of vision Penetrance for gene: FUK were set to Complete Review for gene: FUK was set to AMBER