What are triplet repeats and what is their connection to fragile X syndrome?
Nearly all cases of fragile X syndrome are caused by a mutation in which a DNA segment, known as the CGG triplet repeat, is expanded within the FMR1 gene. Normally, this DNA segment is repeated from 5 to about 40 times. In people with fragile X syndrome, however, the CGG segment is repeated more than 200 times.
How many CGG repeats does fragile X have?
Individuals with Fragile X Syndrome have over 200 CGG repeats. Males with over 200 repeats are almost always affected. Mosaicism, the presence of two different sized repeats or extent of methylation, for pre- and full-mutation alleles has been reported in some individuals with FMR1 full-CGG expansions.
What is the repeat in fragile X?
Cloning of the FMR1 gene revealed that the fragile site of the X chromosome contains a CGG repeat in the 5′ untranslated region (UTR) of the gene. This CGG trinucleotide repeat is unstable, and therefore the repeat length is variable (polymorpyhic) in the normal population, ranging from 6-55 repeats.
Is fragile X syndrome a triplet repeat syndrome or disease?
Fragile X syndrome (FXS), also called Martin-Bell syndrome, is a non-Mendelian trinucleotide repeat disorder. FXS is the most prevalent inherited cause of mild to severe intellectual disability and the most common monogenic cause of autism spectrum disorder (ASD).
What is a triplet repeat disorder?
In summary, triplet repeat disorders are a group of genetic disorders caused by unstable triplet expansion. Because triplet repeat is not stable, these disorders often have high new mutation rate and somatic mosaicism.
What is repeat syndrome?
Trinucleotide repeat disorders, also known as microsatellite expansion diseases, are a set of over 50 genetic disorders caused by trinucleotide repeat expansion, a kind of mutation in which repeats of three nucleotides (trinucleotide repeats) increase in copy numbers until they cross a threshold above which they become …
What is CGG triplet repeat?
One region of the FMR1 gene contains a particular DNA segment known as a CGG trinucleotide repeat, so called because this segment of three DNA building blocks (nucleotides) is repeated multiple times within the gene. In most people, the number of CGG repeats ranges from fewer than 10 to about 40.
What is CGG repeat?
At the beginning of the FMR1 gene there is a repeated sequence of chemical bases, known by the letters CGG. These are repeated a number of times. Most people have less than 55 copies of this CGG repeat. Fragile X premutation carriers can have between 55 and 200 copies of the CGG repeat.
What causes triplet repeat expansion?
Mechanism. Triplet expansion is caused by slippage during DNA replication or during DNA repair synthesis. Because the tandem repeats have identical sequence to one another, base pairing between two DNA strands can take place at multiple points along the sequence.
What causes repeat expansion?
Repeat expansion diseases include both causes of myotonic dystrophy (DM1 and DM2), the most common genetic cause of amyotrophic lateral sclerosis/frontotemporal dementia (C9ORF72), Huntington disease and eight other polyglutamine disorders including the most common forms of dominantly inherited ataxia, the most common …
What is triplet repeat disorders?
Introduction. Trinucleotide repeat disorders consist of a group of human diseases, which are a result of an abnormal expansion of repetitive sequences and primarily affect the nervous system. These occur during various stages of human development.
What is CGG triplet?
What causes the CGG triplet repeat in Fragile X?
Nearly all cases of fragile X syndrome are caused by an alteration (mutation) in the FMR1 gene where a DNA segment, known as the CGG triplet repeat, is expanded. Normally, this DNA segment is repeated from 5 to about 40 times.
When to use trinucleotide repeat analysis for Fragile X?
Trinucleotide repeat analysis is the standard for Fragile X diagnosis. Patients with the above characteristics who had a previously normal cytogenetic Fragile X results should also be considered for trinucleotide repeat analysis. More than 99% of cases are due to the expansion of a polymorphic (CGG) repeat within the FMR1 gene.
What kind of mutation does fragile X syndrome have?
Individuals with fragile X syndrome have a full mutation of the FMR1 allele, with over 200 CGG repeats. In these individuals with a repeat expansion greater than 200, there is methylation of the CGG repeat expansion and FMR1 promoter, leading to the silencing of the FMR1 gene and a lack of its product.
How can you tell if you have fragile X syndrome?
Fragile X syndrome. Diagnosis is by genetic testing to determine the number of CGG repeats in the FMR1 gene. Normal is between 5 and 40 repeats, fragile X syndrome occurs with more than 200, and a premutation is said to be present when a middle number of repeats occurs. Testing for premutation carriers may allow for genetic counseling.