Curation FRA7A ZNF713

Gene ZNF713

Disease FRA7A

Inheritance AD

Score

2 + 0.5 = 2.5 / 18

Genetic + experimental = total

Classification

Limited

Refuted

Moderate

Definitive

Last Updated 08/18/2025

Pubs Reviewed 1

Publication Span 10.32 years

Publication Interval 10.32 years

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 suggestive¹.

All criTRia Curations Locus Page

Genetic evidence

Total: 2

Per page

Category	Type	Citation	Score	Details
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

Per page

Category	Type	Citation	Score	Details
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.

References

Direct supporting references for info on this page.

A CGG-repeat expansion mutation in ZNF713 causes FRA7A: association with autistic spectrum disorder in two families.

Sofie,Metsu, Jacqueline K,Rainger, Kim,Debacker, Birgitta,Bernhard, Liesbeth,Rooms, Daria,Grafodatskaya, Rosanna,Weksberg, Eric,Fombonne, Martin S,Taylor, Stephen W,Scherer, R Frank,Kooy, David R,FitzPatrick

Human mutation · 2014-11-01

pmid:25196122

Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.