Genes in panel
STRs in panel
Prev Next

Genetic epilepsy syndromes

Gene: FBXL4

Green List (high evidence)

FBXL4 (F-box and leucine rich repeat protein 4)
EnsemblGeneIds (GRCh38): ENSG00000112234
EnsemblGeneIds (GRCh37): ENSG00000112234
OMIM: 605654, Gene2Phenotype
FBXL4 is in 12 panels

4 reviews

Rebecca Foulger (Genomics England curator)

I don't know

Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.
Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189

Tracy Lester (Genetics laboratory, Oxford UK)

Green List (high evidence)

AR Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) - characterised by early infantile onset of encephalopathy, hypotoni, lactic acidosis and severe global dev delay. Gai et al, 2013 - 9 children from 7 unrelated families - seizures called a variable feature. Van Rij et al, 2016 - compound het for 2 stop mutations, no mention of epliepsy but died at 2 days of age. Huemer et al, 2015 - retrospecitve review in 28 individuals with FBXL4 defic - 9/28 with epilepsy. Gene reviews Almannai et al, 2017 - seizures in ~33% of cases - fits with Huemer data. Dai et al, 2017 - 10 patients had FBXL4 mutations - 5 no seizures, 2 yes and 3 not applicable (probably due to very early death). Do see epilepsy in ~1/3 but not the major feature of disease.
Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471

Publications

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Changed from Amber to Green. Enough evidence to support gene-disease association and relevance to this panel to rate this gene Green
Created: 13 Nov 2018, 5:44 p.m.
FBXL4 defects are common in patients with congenital lactic acidemia and encephalomyopathic mitochondrial DNA depletion syndrome, seizures are part of the clinical phenotype and can start at age four months (Dai et al 2017 PMID: 27743463). Seizure types reported include complex partial seizures (Baroy et al 2016 PMID:27182039) and absence and generalized seizures (Gai et al 2013 PMID:23993194). The clinical manifestations of FBXL4-Related mtDNA Depletion Syndrome with seizures occurs at a frequency of approximately 33% of cases (Almannai et al 2017 PMID:28383868)
Created: 13 Nov 2018, 5:42 p.m.
Comment on publications: FBXL4-related mtDNA depletion syndrome has been reported in 50 individuals to date. Added publications suggested to support upgrading of the gene to Green.
Created: 13 Nov 2018, 5:34 p.m.
Comment on phenotypes: added OMIM, orphanet phenotype and MIMid
Created: 13 Nov 2018, 5:02 p.m.
Comment on mode of inheritance: Added MOI from external review and checked with PMID
Created: 13 Nov 2018, 5 p.m.

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Seizures are a common feature of this mitochondrial disorder.
Created: 13 Aug 2018, 12:31 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), MIM#615471

Variants in this GENE are reported as part of current diagnostic practice

History Filter Activity

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source Wessex and West Midlands GLH was added to FBXL4.

6 Aug 2019, Gel status: 3

Added New Source

Rebecca Foulger (Genomics England curator)

Source NHS GMS was added to FBXL4.

11 Dec 2018, Gel status: 3

Panel promoted to version 1.0

Sarah Leigh (Genomics England Curator)

Zornitza Stark: Seizures are a common feature

14 Nov 2018, Gel status: 3

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: FBXL4 were changed from Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471 to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471; Seizures

13 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: fbxl4 has been classified as Green List (High Evidence).

13 Nov 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: fbxl4 has been classified as Green List (High Evidence).

13 Nov 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: FBXL4 were set to 23993193; 23993194; 25868664; 26404457; 27182039; 27290639; 27099744; 27743463

13 Nov 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: FBXL4 were set to

13 Nov 2018, Gel status: 2

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: FBXL4 were changed from to Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type), 615471

13 Nov 2018, Gel status: 2

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: FBXL4 was changed from to BIALLELIC, autosomal or pseudoautosomal

25 Jun 2018, Gel status: 2

Added New Source

Sarah Leigh (Genomics England Curator)

Expert Review Amber was added to FBXL4. Panel: Genetic Epilepsy Syndromes

25 Jun 2018, Gel status: 1

Added New Source

Sarah Leigh (Genomics England Curator)

FBXL4 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services

25 Jun 2018, Gel status: 1

Created

Sarah Leigh (Genomics England Curator)

FBXL4 was created by Sarah Leigh