Finding FMR1 mosaicism in Fragile X syndrome.

Objective: Almost all patients with Fragile X Syndrome (FXS) exhibit a CGG repeat expansion (full mutation) in the Fragile Mental Retardation 1 gene (FMR1). Here, the authors report five unrelated males with FXS harboring a somatic full mutation/deletion mosaicism.

Methods: Mutational profiles were only elucidated by using a combination of molecular approaches (CGG-based PCR, Sanger sequencing, MS-MLPA, Southern blot and mPCR).

CGG allele size somatic mosaicism and methylation in FMR1 premutation alleles.

Background: Greater than 200 CGG repeats in the 5'UTR of the FMR1 gene lead to epigenetic silencing and lack of the FMR1 protein, causing fragile X Syndrome. Individual carriers of a premutation (PM) allele with 55-200 CGG repeats are typically unmethylated and can present with clinical features defined as FMR1-associated conditions.

Methods: Blood samples from 17 male PM carriers were assessed clinically and molecularly by Southern blot, western blot, PCR and QRT-PCR.

Transmission of an FMR1 premutation allele in a large family identified through newborn screening: the role of AGG interruptions.

The CGG repeat within the premutation range in the fragile X mental retardation 1 (FMR1) gene can lead to neurodegenerative disorders and intellectual disabilities. An increase in size upon the transmission from parent to child is more likely to occur for larger alleles and without AGG interruptions. We describe the molecular structure and the transmission of an FMR1 premutation allele in a multigenerational family, identified through newborn screening for fragile X syndrome.

Immune-mediated disorders among women carriers of fragile X premutation alleles.

The relative risk of immune-mediated disorders (IMDs) among women carriers of premutation alleles is estimated by a survey for IMDs among 344 carrier women (age 19-81 years; mean 46.35 and SD 12.60) and 72 controls (age 18-87 years; mean 52.