Intellectual disability syndromic and non-syndromic
Gene: FGF13

FGF13 (fibroblast growth factor 13)
EnsemblGeneIds (GRCh38): ENSG00000129682
EnsemblGeneIds (GRCh37): ENSG00000129682
OMIM: 300070, Gene2Phenotype
FGF13 is in 3 panels

1 review

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

PMID 34184986: 3 individuals reported with moderate to severe ID and maternally inherited 5' variant c.-32C-G
Created: 19 Jan 2023, 10:51 p.m. | Last Modified: 19 Jan 2023, 10:51 p.m.

Panel Version: 0.5154

Two sibling pairs and three unrelated males reported who presented in infancy with intractable focal seizures and severe developmental delay. The variants were located in the N-terminal domain of the A isoform of FGF13/FHF2 (FHF2A). The X-linked FHF2 gene (also known as FGF13) has alternative first exons which produce multiple protein isoforms that differ in their N-terminal sequence. The variants were located at highly conserved residues in the FHF2A inactivation particle that competes with the intrinsic fast inactivation mechanism of Nav channels. Functional characterization of mutant FHF2A co-expressed with wild-type Nav1.6 (SCN8A) revealed that mutant FHF2A proteins lost the ability to induce rapid-onset, long-term blockade of the channel while retaining pro-excitatory properties. These gain-of-function effects are likely to increase neuronal excitability consistent with the epileptic potential of FHF2 variants.
Sources: Literature
Created: 7 Jan 2021, 3:46 a.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Developmental and epileptic encephalopathy 90, MIM# 301058; Intellectual developmental disorder, X-linked 110, MIM# 301095

Publications

Mode of pathogenicity
Other

Created: 7 Jan 2021, 3:46 a.m.

Panel version: 0.5154

Details

Mode of Inheritance

X-LINKED: hemizygous mutation in males, biallelic mutations in females

Sources

Expert Review Green
Literature

Phenotypes

Developmental and epileptic encephalopathy 90, MIM# 301058
Intellectual developmental disorder, X-linked 110, MIM# 301095

Tags

5'UTR

OMIM

300070

Clinvar variants

Variants in FGF13

Penetrance

None

Publications

Mode of Pathogenicity

Other

Panels with this gene