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A CGG ‐Repeat Expansion Mutation in ZNF 713 Causes FRA 7 A : Association with Autistic Spectrum Disorder in Two Families
Author(s) -
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.
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22683
Subject(s) - biology , association (psychology) , genetics , mutation , autistic spectrum , autistic spectrum disorder , spectrum (functional analysis) , autism , psychiatry , medicine , psychology , physics , gene , quantum mechanics , psychotherapist
We report de novo occurrence of the 7p11.2 folate‐sensitive fragile site FRA 7 A in a male with an autistic spectrum disorder ( ASD ) due to a CGG ‐repeat expansion mutation (∼450 repeats) in a 5′ intron of ZNF 713 . This expanded allele showed hypermethylation of the adjacent C p G island with reduced ZNF 713 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 FRA 7 A premutations, which were partially or mosaically methylated. In one of the affected siblings, mitotic instability of the premutation was observed. ZNF 713 expression in LCL s 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.