Affected individuals have >200 CGG repeats and are classified as having a full mutation (FM) which is associated with hypermethylation of an upstream gene promoter region (CpG island) and silencing of FMR-1 gene transcription which results in the absence of the gene product, fragile X mental retardation protein (FMRP).
Both males and females with a PM in FMR-1 have an increased risk of developing FXTAS, a progressive neurodegenerative disorder with a prevalence of 45% reported in males older than 50 years of age.
The FMR-1 gene, identified in 1991, is 38 kb long and consists of 17 exons which are alternatively spliced.
Currently, testing is performed by duplex polymerase chain reaction (PCR) analysis to size the normal and lower PM FMR-1 alleles, followed by Southern blotting to confirm expansions.
To review and analyse the findings from DNA testing for diagnostic, carrier and prenatal purposes for FXS and other FMR-1 -related disorders, conducted at the DHG over a 20-year period.
A total of 2 690 individuals from 2 243 families underwent genetic testing for FXS and other FMR-1 -associated disorders through the DHG during the 20-year period (January 1992-July 2012).
Southern blot analysis was performed to establish the methylation status of the promoter region, to detect FMs that failed to amplify on PCR analysis and to differentiate females who were homozygous for a normal-sized FMR-1 allele from female PM/FM heterozygotes.
Eight of the 17 (47%) fetuses had an FMR-1 FM (five male and three female), two a PM (one male and one female) and seven (41%) tested negative.
Female siblings with FMR-1 expansions of both alleles
and Dutch researchers found that people with fragile X syndrome -- the most common inherited cause of mental retardation -- bear repetitive DNA segments in a gene they named FMR-1
, for fragile X mental retardation-1 (SN: 6/8/91, p.
Although they have not yet discovered the gene's normal function, they note that certain stretches of FMR-1
are duplicated many times over in silent carriers and in patients with fragile X syndrome.