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Epigenetics of fragile X syndrome and fragile X‐related disorders
Author(s) -
Kraan Claudine M,
Godler David E,
Amor David J
Publication year - 2019
Publication title -
developmental medicine and child neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.658
H-Index - 143
eISSN - 1469-8749
pISSN - 0012-1622
DOI - 10.1111/dmcn.13985
Subject(s) - fragile x syndrome , epigenetics , dna methylation , genetics , fragile x , fmr1 , allele , autism , gene silencing , untranslated region , biology , gene , bioinformatics , medicine , psychiatry , gene expression , messenger rna
The fragile X mental retardation 1 gene ( FMR 1 )‐related disorder fragile X syndrome ( FXS ) is the most common heritable form of cognitive impairment and the second most common cause of comorbid autism. FXS usually results when a premutation trinucleotide CGG repeat in the 5′ untranslated region of the FMR 1 gene ( CGG 55–200) expands over generations to a full mutation allele ( CGG >200). This expansion is associated with silencing of the FMR 1 promoter via an epigenetic mechanism that involves DNA methylation of the CGG repeat and the surrounding regulatory regions. Decrease in FMR 1 transcription is associated with loss of the FMR 1 protein that is needed for typical brain development. The past decade has seen major advances in our understanding of the genetic and epigenetic processes that underlie FXS . Here we review these advances and their implications for diagnosis and treatment for individuals who have FMR 1 ‐related disorders. What This Paper Adds Improved analysis of DNA methylation allows better epigenetic evaluation of the fragile X gene. New testing techniques have unmasked interindividual variation among children with fragile X syndrome. New testing methods have also detected additional cases of fragile X.