This report describes developmental and epileptic encephalopathy 47, an early infantile subtype of developmental and epileptic encephalopathy that exhibits autosomal dominant or recessive inheritance. The human gene implicated is FGF12, which encodes fibroblast growth factor 12. There is one moderate-scoring fly ortholog, Dmel\bnl, for which amorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Additionally, a construct reflecting a variant implicated in disease, Dmel\bnl;pE324K (orthologous to Hsap\FGF12;p.E87K) has been generated. See the 'Disease-Implicated Variants' table below.
A wild-type construct of human Hsap\FGF12 has been introduced into flies, but has not been analyzed in the context of DEE47.
Trachael-specific overexpression of wild-type Dmel\bnl results in defects in the structure of dorsal trunk trachea, while overexpression of Dmel\bnl bearing the disease-implicated variant show no tracheal defects, suggesting the variant is a loss-of-function variant.
[updated Apr. 2024 by FlyBase; FBrf0222196]
[DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 47; DEE47](https://omim.org/entry/617166)
[FIBROBLAST GROWTH FACTOR 12; FGF12](https://omim.org/entry/601513)
Developmental and epileptic encephalopathy 47 (DEE47) is a neurologic disorder characterized by onset of intractable seizures in the first days or weeks of life. EEG shows background slowing and multifocal epileptic spikes, and may show hypsarrhythmia. Most patients have developmental regression after seizure onset and show persistent intellectual disability and neurologic impairment, although the severity is variable. Treatment with phenytoin, a voltage-gated sodium channel blocker, may be beneficial (summary by Guella et al., 2016; pubmed:27872899). [from MIM:617166; 2023.07.19]
Biallelic (autosomal recessive) cases of developmental and epileptic encephalopathy 47 have been reported (Ohori, et al., 2003; pubmed:37286232; FBrf0256751).
Developmental and epileptic encephalopathy 47 (DEE47) is caused by heterozygous mutation in the FGF12 gene (601513) on chromosome 3q28. [from MIM:617166; 2023.03.21]
The FGF12 gene encodes a member of the fibroblast growth factor homologous factor (FHF) family, which are small cytosolic proteins that interact with the cytoplasmic tails of voltage-gated sodium channels and elevate the voltage dependence of neuronal sodium channel fast inactivation (summary by Siekierska et al., 2016; pubmed:27164707). [from MIM:601513; 2023.07.19]
Many to one (many human to 1 Drosophila); FGF12 has one moderate-scoring Drosophila ortholog, bnl.
Moderate-scoring ortholog of human FGF16, FGF12, and others (1 Drosophila to many human).
