FRA7A_ZNF713
- Gene
- ZNF713
- Disease
- FRA7A
- Inheritance
- AD
- Classification
- Limited
- Total Score
- 2.5
- Publications Reviewed
- 1
- Publication Span
- 10.32 years
- Last Updated
- 08/18/2025
- Curator(s)
- Laurel Hiatt, Macayla Weiner, Harriet Dashnow
Description
A CGG repeat expansion within the first intron/5' region of ZNF713 underlies the folate-sensitive fragile site FRA7A. A de novo full expansion (>450 repeats) was identified in a male with autism spectrum disorder (ASD), associated with CpG island hypermethylation and reduced ZNF713 expression in patient-derived lymphoblastoid cell lines (LCLs). In a second family, three ASD-affected siblings carried paternal premutation alleles (~42–85 repeats) showing mitotic instability, partial/mosaic methylation, and variable ZNF713 expression including overexpression. Control screening identified only normal alleles (5–22 repeats) in 176 individuals and no additional FRA7A cases in >9,000 cytogenetic analyses. While the repeat expansion demonstrates molecular features consistent with other CGG-repeat disorders, the causal relationship with ASD remains suggestive [@pmid:25196122].
Genetic evidence
Total: 2
| Singular Evidence | Probands | PMID:25196122 | 1.5 | Two unrelated families described. Family 7,792 included one proband with a maternally derived full CGG expansion (>450 repeats), FRA7A fragile site, CpG methylation, and reduced ZNF713 expression. Family TCAG0070 included three ASD-affected siblings carrying paternal premutation alleles with evidence of instability, mosaicism, and variable gene expression. |
| Collective Evidence | Segregation | PMID:25196122 | 0.5 | Premutation alleles segregate with ASD in three siblings in one family, but are also present in an unaffected father, indicating reduced penetrance or tissue-specific effects. No full or premutation alleles were observed in controls, however they note that the assay is subject to allelic dropout. No additional FRA7A cases were detected in >9,000 neurodevelopmental cytogenetic analyses. Score is reduced from default because of the small number of individuals, presence of premutation alleles in an unaffected parent, and potential assay limitations. |
Experimental evidence
Total: 0.5
| Function | Regulatory impact | PMID:25196122 | 0.5 | Full expansion allele shows hypermethylation and ~60% reduction of ZNF713 expression in proband LCLs, consistent with repeat-mediated silencing. |
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.