Relevance to Autism

Fry et al., 2021 demonstrated that missense variants in the N-terminal domain of the A isoform of the FGF13 gene caused an X-linked developmental and epileptic encephalopathy (developmental and epileptic encephalopathy-90; OMIM 301058); all seven affected individuals in this report (two sibling pairs and three unrelated males) presented with intractable focal seizures and severe-profound developmental delay/intellectual disability, and four individuals were diagnosed with autism spectrum disorder. Furthermore, functional characterization of FGF13 missense variants in this report revealed that mutation proteins lost the ability to induce rapid-onset, long-term blockade of wild-type Nav1.6 (SCN8A) channels while retaining pro-excitatory properties, consistent with a gain-of-function effect. Application of sdMAF separately to ASD individual and control cohorts in an X-chromosome-wide association study of 6,873 individuals with autism from MSSNG, SSC, and SPARK (5,639 males and 1,234 females) and 8,981 controls (3,911 males and 5,070 females) in Mendes et al., 2025 identified a statistically significant region including the FGF13 gene in which all SNPs exhibited higher MAFs in males than females [the lead SNP for this region (rs555083289) had a sdMAF P-value of 1.19E-05].

Molecular Function

The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. This gene is located in a region on chromosome X, which is associated with Borjeson-Forssman-Lehmann syndrome (BFLS), making it a possible candidate gene for familial cases of the BFLS, and for other syndromal and nonspecific forms of X-linked cognitive disability mapping to this region.

External Links

References