Methylation premutation gene contains trinucleotide repeat expansion. Medical search. Frequent questions

Fragile X is usually caused by a trinucleotide expansion in the FMR1 gene on the X chromosome. (uab.edu)
If a homozygous female, premutation, or full mutation is identified or suspected, a second tier of testing consists of Eco RI and Eag I restriction digest followed by Southern blot analysis using the DNA probe, StB12.3 to determine methylation status of the FMR1 gene and approximate number of trinucleotide repeats. (uab.edu)
other mutations involving the FMR1 gene can cause FXS if they prevent production or alter functional domains of the encoded protein, the fragile X mental retardation protein (FMRP) ( O'Donnell and Warren, 2002 ). (jneurosci.org)
Negative association findings and research involving the serotonin transporter gene, FMR1, RELN, WNT2, HOXA1, and HOXB1 genes may be found elsewhere on this site . (neurotransmitter.net)

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 cause developmental, neurological or neuromuscular disorders. (wikipedia.org)
Individuals with pre-mutation alleles have 59-230 repeats whereas individuals with intermediate sized alleles ("gray zone" alleles) have 41-58 repeats, broadly defined. (uab.edu)
METHOD: Mutation screening of positional candidate genes was performed in two stages. (neurotransmitter.net)

The first trinucleotide repeat disease to be identified was fragile X syndrome, which has since been mapped to the long arm of the X chromosome. (wikipedia.org)
The second DNA-triplet repeat disease, fragile X-E syndrome, was also identified on the X chromosome, but was found to be the result of an expanded CCG repeat. (wikipedia.org)
Fragile X cases have more than 200 repeats of the trinucleotide CGG at a fragile locus of the X chromosome (Xq27.3) which affords the basis of the molecular diagnosis of the syndrome. (omicsonline.org)

The discovery that trinucleotide repeats could expand during intergenerational transmission and could cause disease was the first evidence that not all disease-causing mutations are stably transmitted from parent to offspring. (wikipedia.org)
The decision to rescreen a patient should be undertaken only with the guidance of a genetics professional who can best assess the incremental benefit of repeat testing for additional mutations. (acog.org)
We hypothesize that there might be at least three types of autism susceptibility genes/mutations that can be (i) specific to an individual patient or family, (ii) in a genetically isolated sub-population and (iii) a common factor shared amongst different populations. (neurotransmitter.net)
The genes/mutations could act alone or interact with other genetic and/or epigenetic or environmental factors, causing autism or related disorders. (neurotransmitter.net)

Patients carry from 230 to 4000 CGG repeats in the gene that causes fragile X syndrome, while unaffected individuals have up to 50 repeats and carriers of the disease have 60 to 230 repeats. (wikipedia.org)
Since FXS cannot always be identified by cytogenetic analysis, molecular testing of the fragile X mental retardation 1 CGG repeat was performed in 440 samples. (wjgnet.com)

Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism. (neurotransmitter.net)
In the present study, genes across the 2q24-q33 interval were analyzed to identify an autism susceptibility gene in this region. (neurotransmitter.net)
CONCLUSIONS: A strong association of autism with SNPs within the SLC25A12 gene was demonstrated. (neurotransmitter.net)

Many regions of the genome (exons, introns, intergenic regions) normally contain trinucleotide sequences, or repeated sequences of one particular nucleotide, or sequences of 2, 4, 5 or 6 nucleotides. (wikipedia.org)
The first stage involved identifying, in unrelated subjects showing linkage to 2q24-q33, genetic variants in exons and flanking sequence within candidate genes and comparing the frequency of the variants between autistic and unrelated nonautistic subjects. (neurotransmitter.net)

The chromosomal instability resulting from this trinucleotide expansion presents clinically as intellectual disability, distinctive facial features, and macroorchidism in males. (wikipedia.org)

However, the frequency of occurrence of any one particular repeat sequence disorder varies greatly by ethnic group and geographic location. (wikipedia.org)

In this second type of disorder, large repeat expansions in DNA are transcribed into pathogenic RNAs that form nuclear RNA foci. (wikipedia.org)
Carrier screening is a term used to describe genetic testing that is performed on an individual who does not have any overt phenotype for a genetic disorder but may have one variant allele within a gene(s) associated with a diagnosis. (acog.org)

These individuals are referred to as "premutation carriers. (wikipedia.org)

Sometimes, a person may have more than the usual number of copies of a repeat sequence associated with a gene, but not enough to alter the function of that gene. (wikipedia.org)

Polymerase chain reaction analysis is used as a first tier test to define the repeat size. (uab.edu)
Polymerase chain reaction analysis is used to further define the repeat number more precisely. (uab.edu)

The epigenetic alterations and their effects are described more fully by Barbé and Finkbeiner These authors cite evidence that the age at which an individual begins to experience symptoms, as well as the severity of disease, is determined both by the size of the repeat and the epigenetic state within the repeat and around the repeat. (wikipedia.org)

The first main category these authors discuss is repeat expansions located within the promoter region of a gene or located close to, but upstream of, a promoter region of a gene. (wikipedia.org)

Two single nucleotide polymorphisms (SNPs) that showed evidence for divergent distribution between autistic and nonautistic subjects were identified, both within SLC25A12, a gene encoding the mitochondrial aspartate/glutamate carrier (AGC1). (neurotransmitter.net)

FXPOI, defined as hypergonadotropic hypogonadism before age 40 years, has been observed in 20% of women who carry a premutation allele compared to 1% in the general population. (nih.gov)
The underlying full mutations arise exclusively on transmission from a mother who carries a premutation allele (60-200 CGGs). (bmj.com)
1-3 Disease alleles, containing more than 220 CGG triplets and designated full mutations, only arise upon transmission from a mother who carries a premutation allele that is characterised by repeat sizes between 60 and 200 and is not associated with intellectual deficits. (bmj.com)
While several genes affected by the expansion have been identified, the prevalence, risk factors, and nature of the high allele repeats, as well as the mechanism and timing of repeat amplifications in various populations, need further study. (nih.gov)
Is the 31 CAG repeat allele of the spinocerebellar ataxia 1 (SCA1) gene locus non-specifically associated with trinucleotide expansion diseases? (cdc.gov)
Of the 2 239 patients who had diagnostic FMR-1 testing, 128 (5.7%) had a full mutation, 12 (0.5%) had a premutation and 43 (1.9%) an intermediate allele. (samj.org.za)

The first trinucleotide repeat disease to be identified was fragile X syndrome, which has since been mapped to the long arm of the X chromosome. (wikipedia.org)
Patients carry from 230 to 4000 CGG repeats in the gene that causes fragile X syndrome, while unaffected individuals have up to 50 repeats and carriers of the disease have 60 to 230 repeats. (wikipedia.org)
We know that premutation carriers have a higher risk of anxiety and depression but it has not been known whether this is related to the stress of having a child with fragile X syndrome or whether it has an actual genetic basis. (medscape.com)
Expanded trinucleotide repeats are associated with several neuropsychiatric disorders, including fragile X syndrome (FraX) which is the most common inherited form of mental retardation. (ox.ac.uk)
Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. (org.ua)
Inheritance of the fragile X syndrome: size of the fragile X premutation is a major determinant of the transition to full mutation. (org.ua)
Fragile X syndrome (FXS), the most common inherited cause of intellectual disability (ID) worldwide, is caused by the expansion of a CGG repeat in the fragile X mental retardation gene ( FMR-1 ) gene. (samj.org.za)

These premutation alleles may become unstable, only through maternal transmission, with further expansion in the next generations. (nih.gov)
With increasing population doublings, expansion patterns changed and showed accumulation of shorter alleles. (bmj.com)
Analysis of the Fragile X Trinucleotide Repeat in Basques: Association of Premutation and Intermediate Sizes, Anchoring AGGs and Linked Microsatellites with Unstable Alleles. (cdc.gov)
Intermediate (IM) alleles ('gray zone') range from 45 to 54 CGG repeats. (samj.org.za)

These individuals are referred to as "premutation carriers. (wikipedia.org)
Some carriers, during the formation of eggs or sperm, may give rise to higher levels of repetition of the repeat they carry. (wikipedia.org)
Individuals with expanded repeat lengths varying from 50 to 200 repeats do not exhibit the classical FXS phenotype, but are considered as fragile X premutation (PM) carriers. (nih.gov)
For long-time, male and female premutation carriers were considered as asymptomatic. (nih.gov)
Far more common are carriers of a lesser change in the fragile X gene characterized by 55 to 199 repeats of the CGG trinucleotide. (medscape.com)
Fragile X premutation carriers have normal intellect, but they are more likely to develop social anxiety and depression. (medscape.com)
The researchers conducted a study in female carriers of the premutation suggesting that their risk for social anxiety and depression correlates to the degree of methylation of the gene, which can be detected with a blood test. (medscape.com)
Pre-mutation carriers of FraX (with 55-200 CGG trinucleotide repeats) were originally considered unaffected, although recent studies challenge this view. (ox.ac.uk)
Within pre-mutation carriers of FraX, ageing, increases in the number of CGG trinucleotide repeats and decreases in %FMRP(+) lymphocytes were associated with decreasing voxel density of regions previously identified as decreased relative to controls. (ox.ac.uk)
[12] Fisch GS, Snow K, Thibodeau SN, Chalifaux M, Holden JJ, Nelson DL, Howard-Peebles PN, Maddalena A. The fragile X premutation in carriers and its effect on mutation size in offspring. (org.ua)
Premutation (PM) carriers have expansions of 55 to 200 repeats, which are not associated with ID. (samj.org.za)

Expansion of this repeat region greater than 200 repeats leads to methylation-coupled silencing of the gene and absence of the Fragile X mental retardation protein (FMRP), causing the classical FXS. (nih.gov)
Distribution of fragile X mental retardation 1 CGG repeat and flanking haplotypes in a large Chinese population. (cdc.gov)
Almost all cases of FXS are caused by the expansion of a CGG repeat in the 5' untranslated region of the fragile X mental retardation gene ( FMR-1 ) (OMIM #309550) at the FRAXA fragile site Xq27.3. (samj.org.za)
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). (samj.org.za)

The third main category of trinucleotide repeat disorders and related microsatellite disorders is due to the translation of repeat sequenced into pathogenic proteins containing a stretch of repeated amino acids. (wikipedia.org)
Proteins whose function is altered by interaction with the products of these genes need to be identified and the nature of the interaction further clarified. (nih.gov)

Increase of FMRP expression, raised levels ofFMR1 mRNA, and clonal selection in proliferating cells with unmethylated fragile X repeat expansions: a clue to the sex bias in the transmission of full mutations? (bmj.com)

Argonaute-2-dependent rescue of a Drosophila model of FXTAS by FRAXE premutation repeat. (nih.gov)
Polymorphism of trinucleotide repeats at loci FRAXA and FRAXE in the population of Tomsk]. (cdc.gov)

The chromosomal instability resulting from this trinucleotide expansion presents clinically as intellectual disability, distinctive facial features, and macroorchidism in males. (wikipedia.org)
Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. (org.ua)

200 CGG repeats) while the diagnosis of FXTAS or FXPOI is associated with a premutation -sized repeat (55-200 CGG repeats). (nih.gov)

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 cause developmental, neurological or neuromuscular disorders. (wikipedia.org)
For the study, researchers compared 35 women who had the premutation with 35 women who did not have this genetic change. (medscape.com)
These results are exciting because it means we could use an easily accessible blood test to help diagnose people who have the premutation genetic abnormality and identify who is more likely to have problems and begin early treatment," said lead study author Kim M. Cornish, PhD, from Monash University in Victoria, Australia. (medscape.com)
This study suggests that there is a genetic basis for these issues and we have a blood test that can detect which patients with this premutation are likely to have a higher risk of developing these problems. (medscape.com)

This view was, however, gradually challenged with the description and reports of different premutation-associated clinical phenotypes over the last decade. (nih.gov)
She noted that for the first decade following the discovery of the fragile X gene this premutation was assumed to have no clinical impact, but recently other disorders have also been discovered in some of these individuals that have a biological basis. (medscape.com)
Further correlation of the degree of expansion and expression of clinical manifestations of the fragile X phenotype, particularly behavioral manifestations such as autism, autism spectrum disorders, attention deficit hyperactivity disorder (ADHD), and anxiety disorders, is needed. (nih.gov)

Translation of these repeat expansions occurs mostly through two mechanisms. (wikipedia.org)
This is known as a premutation and occurs in up to 1 in 450 men and 1 in 150 women. (medscape.com)

Trinucleotide repeats are a subset of a larger class of unstable microsatellite repeats that occur throughout all genomes. (wikipedia.org)

To address these questions experimentally, we used a model system of cultured fibroblasts from a male who presented heterogeneous unmethylated expansions in the pre- and full mutation size range. (bmj.com)

The first main category these authors discuss is repeat expansions located within the promoter region of a gene or located close to, but upstream of, a promoter region of a gene. (wikipedia.org)

Future studies could investigate whether early intervention with cognitive training to improve executive function leads to remediation effects for social anxiety, particularly in premutation females within the higher risk group," she added. (medscape.com)

Comparative (computational) analysis of the DNA methylation status of trinucleotide repeat expansion diseases. (cdc.gov)

Many regions of the genome (exons, introns, intergenic regions) normally contain trinucleotide sequences, or repeated sequences of one particular nucleotide, or sequences of 2, 4, 5 or 6 nucleotides. (wikipedia.org)
It should be noted that typical multigene panels and comprehensive genomic testing ( exome or genome sequencing ) are useful only when no CGG repeat expansion is detected but FXS is still suspected. (nih.gov)

These repeats are able to promote localized DNA epigenetic changes such as methylation of cytosines. (wikipedia.org)
The epigenetic alterations and their effects are described more fully by Barbé and Finkbeiner These authors cite evidence that the age at which an individual begins to experience symptoms, as well as the severity of disease, is determined both by the size of the repeat and the epigenetic state within the repeat and around the repeat. (wikipedia.org)

The full mutation in the FMR-1 gene of male fragile X patients is absent in their sperm. (org.ua)
Targeted next-generation sequencing of 54 genes revealed 17 genes that were recurrently mutated in >5% of patients. (bvsalud.org)

This results in, variously, a toxic gain of function, a loss of function, a dominant negative effect and/or a mix of these mechanisms for the protein hosting the expansion. (wikipedia.org)
Mechanisms by which the expression of these genes is dysregulated, e.g., by methylation and acetylation, also need further study. (nih.gov)

FMR-1 CGG repeat distribution analysis in 1 532 males negative for the FMR-1 expansion showed that 29 and 30 CGG repeats were the most common (61.1%), but the distribution was significantly different in the black and white populations. (samj.org.za)

However, there are few studies on the effect of pre-mutation trinucleotide repeat expansion on the male human brain using quantitative MRI. (ox.ac.uk)

3 8 De novo methylation is thought to be initiated at embryogenesis by attraction of DNA methyl transferase to hairpin-like unimolecular fold backs of CGG repeat sequences expanded beyond a threshold of repeat length. (bmj.com)

The women with the premutation who had high methylation levels were more likely to have depression, social anxiety, and problems with executive functioning skills. (medscape.com)

She also pointed out that difficulties with executive functioning appear to be the mediator between the degree of methylation and the social anxiety problems. (medscape.com)

this relationship was not seen in the women who did not have the premutation. (medscape.com)

The FMR-1 CGG repeat distribution varied from that found in other studies. (samj.org.za)

In general, the larger the expansion the faster the onset of disease, and the more severe the disease becomes. (wikipedia.org)

Trinucleotide repeat disorders and the related microsatellite repeat disorders affect about 1 in 3,000 people worldwide. (wikipedia.org)

Sometimes, a person may have more than the usual number of copies of a repeat sequence associated with a gene, but not enough to alter the function of that gene. (wikipedia.org)
The second main category of trinucleotide repeat disorders and related microsatellite disorders involves a toxic RNA gain of function mechanism. (wikipedia.org)

Anatomy4

Organisms2

Diseases22

Chemicals and Drugs19

Analytical, Diagnostic and Therapeutic Techniques and Equipment9

Psychiatry and Psychology2

Phenomena and Processes36

Information Science3

Health Care2

FMR14

Mutation3

Chromosome3

Mutations4

Fragile2

Autism3

Exons2

Intellectual1

Frequency1

Disorder2

Individuals1

Sequence1

Analysis2

Size1

Region1

Carrier1

Allele6

Fragile X syndro7

Alleles4

Carriers11

Mental retardation4

Proteins2

FMRP1

FRAXE2

Instability2

FXTAS1

Genetic4

Clinical3

Occurs2

Unstable1

Mutation size1

Promoter1

Females1

Diseases1

Genome2

Epigenetic2

Patients2

Mechanisms2

Males1

Male1

Sequences1

High1

Degree1

Women1

Distribution1

General1

Worldwide1

Function2