A CGG‐Repeat Expansion Mutation in ZNF713 Causes FRA7A: Association with Autistic Spectrum Disorder in Two Families. Issue 11 (November 2014)

• Record Type: Journal Article
• Authors: Metsu, Sofie; Rainger, Jacqueline K.; Debacker, Kim; Bernhard, Birgitta; Rooms, Liesbeth; Grafodatskaya, Daria; Weksberg, Rosanna; Fombonne, Eric; Taylor, Martin S.; Scherer, Stephen W.; Kooy, R. Frank; FitzPatrick, David R.
• Is Part Of: Human mutation. Volume 35:Issue 11(2014:Nov.)
• Page Start: 1295
• Page End: 1300
• Publication Date: 2014-11
• Subjects: Human chromosome abnormalities -- Periodicals; Mutation (Biology) -- Periodicals; 616.04205
• DOI: 10.1002/humu.22683
• Languages: English
• ISSNs: 1059-7794

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>We report de novo occurrence of the 7p11.2 folate‐sensitive fragile site FRA7A in a male with an autistic spectrum disorder (ASD) due to a CGG‐repeat expansion mutation (∼450 repeats) in a 5′ intron of <italic>ZNF713</italic>. This expanded allele showed hypermethylation of the adjacent CpG island with reduced <italic>ZNF713</italic> expression observed in a proband‐derived lymphoblastoid cell line (LCL). His unaffected mother carried an unmethylated premutation (85 repeats). This CGG‐repeat showed length polymorphism in control samples (five to 22 repeats). In a second unrelated family, three siblings with ASD and their unaffected father were found to carry FRA7A premutations, which were partially or mosaically methylated. In one of the affected siblings, mitotic instability of the premutation was observed. <italic>ZNF713</italic> expression in LCLs in this family was increased in three of these four premutation carriers. A firm link cannot yet be established between ASD and the repeat expansion mutation but plausible pathogenic mechanisms are discussed.</p> </abstract>