Fragile X syndrome in a male with methylated premutation alleles and no detectable methylated full mutation alleles
Year: 2019
Type: article
Study design: Case Report
Abstract: Most cases of fragile X syndrome (FXS) result from aberrant methylation of the FMR1 gene. Methylation occurs when the number of tandemly arranged cytosine guanine guanine (CGG)-repeats in the 5' end of the transcriptional unit of FMR1 exceeds a certain critical threshold, thought to be between 200 and 400 repeats. Such alleles are referred to as full mutation (FM) alleles. Premutation (PM) alleles, alleles with 55-200 repeats, are generally not aberrantly methylated and in fact may have hyperexpression of the FMR1 mRNA. We describe here a male who meets the diagnostic criteria for FXS, who is highly mosaic with a mixture of multiple PM and FM alleles and 50% methylation. However, the methylated alleles are limited to two alleles in the PM range, ~165 and ~175 repeats respectively, with the FM alleles being unmethylated. This finding has implications for FXS diagnosis as well as for efforts to delete the repeat in individuals with FXS using a CRISPR-Cas9 approach.
DOI: 10.1002/ajmg.a.61286
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: Disease pathology in the Fragile X-associated disorders, Gene silencing in Fragile X syndrome, G3033763348, Dysregulation of Protein Synthesis in Fragile X Syndrome and Other Developmental Disorders, G5289084419, The consequences of repeat expansion in the Fragile X-related disorders, G9000036738, Understanding the mutational mechanism responsible for the Repeat Expansion Diseases
OpenAlex ID: W2965117567