Methylated premutation of the FMR1 gene in three sisters: correlating CGG expansion and epigenetic inactivation.

ABSTRACT: Fragile X syndrome (FXS) is a very frequent cause of inherited intellectual disability (ID) and autism. Most FXS patients have an expansion over 200 repeats of (CGG)_n sequence ("full mutation" (FM)) located in the 5'UTR of the FMR1 gene, resulting in local DNA methylation (methylated "full mutation" (MFM)) and epigenetic silencing. The absence of the FMRP protein is responsible for the clinical phenotype of FXS. FM arises from a smaller maternal allele with 56-200 CGG repeats ("premutation" (PM)) during maternal meiosis. Carriers of PM alleles, which are typically unmethylated, can manifest other clinical features (primary ovarian insufficiency (POI) or FXS-associated tremor-ataxia syndrome (FXTAS)), known as fragile X-related disorders. In FXS families, rare males who have inhe

SUBMITTER: Tabolacci E 

PROVIDER: S-EPMC7171171 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature