Length of uninterrupted CGG repeats determines instability in the FMR1 gene

Eichler, Evan E.; Holden, Jeanette J. A.; Popovich, Bradley W.; Reiss, Allan L.; Snow, Karen; Thibodeau, Stephen N.; Richards, C. Sue; Ward, Patricia A.; Nelson, David L.

doi:10.1038/ng0994-88

Cited by 432 publications

(409 citation statements)

References 33 publications

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“…24 The vast majority of alleles with o45 CGG in the general population have repeat tracks with two AGG interruptions, and repeat instabilities are rare for these alleles. Data reported in the literature show that IA present similar proportions of unstable transmissions.…”

Section: Discussionmentioning

confidence: 99%

Intermediate FMR1 alleles and cognitive and/or behavioural phenotypes

et al. 2011

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During the last few years, several studies have reported an excess of intermediate FMR1 alleles in patients with cognitive and/or behavioural phenotypes. Here, we report the frequency of intermediate alleles (IAs) in three pathologies, intellectual disabilities (IDs), attention-deficit/hyperactivity disorder and autism, from different Spanish regions. We found 142 IAs among 9015 patients with ID (1.6%), 4 among the 415 ADHD patients (0.96%) and 4 among the 300 autistic patients (1.3%), similar to the frequency reported in our control population. No evidence was found of an excess of IA at the FRAXA locus in any of the study populations, although geographical variability was detected. Moreover, the analysis of 100 transmissions of IAs showed that 95% of these alleles were stable. Only 3% expanded within the same range and 2% expanded to a full mutation in two generations. No evidence of an association between IAs and behavioural or cognitive phenotypes was found, suggesting that IAs are not clearly implicated in these pathologies.

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Section: Discussionmentioning

confidence: 99%

Intermediate FMR1 alleles and cognitive and/or behavioural phenotypes

et al. 2011

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“…In the absence of a family history of fragile X, however, risk assessments are problematic because some newly identified intermediate and small premutation alleles are stably inherited. 9 In 1994, Eichler et al 11 suggested that AGGs interspersed within the FMR1 repeat region increase its stability. In the general population, 94% of alleles have one or two AGG interruptions, which are most commonly observed on the 5′ end of the repeat tract as the 10 th or 11 th and 20 th or 21 st triplet of the repeat.…”

Section: Introductionmentioning

confidence: 99%

Fragile X full mutation expansions are inhibited by one or more AGG interruptions in premutation carriers

Nolin

Glicksman

Ersalesi

et al. 2015

Genetics in Medicine

121

131

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AGGs. Two contractions in maternal transmission were accompanied by loss of AGGs, suggesting a mechanism for generating alleles that lack AGG interruptions. Maternal age was examined as a factor in full mutation expansions using prenatal samples to minimize ascertainment bias, and a possible effect was observed though it was not statistically significant (P = 0.06). Conclusion:These results strengthen the association of AGG repeats with CGG repeat stability and provide more accurate risk estimates of full mutation expansions for women with 45-90 repeat alleles.

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“…In intermediate and premutation alleles the AGG interruptions tend to occur at the 5' end of the locus and the pure CGG stretch, defined as the longest stretch of uninterrupted CGG repeats, is located at the 3' end (8,9). The loss of AGG interruptions appear to have occurred multiple times during human evolution (10) but can be a late event in the mutation pathway that leads to expansion (11).…”

Section: Introductionmentioning

confidence: 99%

Distribution of AGG interruption patterns within nine world populations

Yrigollen

Sweha

Durbin‐Johnson

et al. 2014

IRDR

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The CGG trinucleotide repeat within the FMR1 gene is associated with multiple clinical disorders, including fragile X-associated tremor/ataxia syndrome, fragile X-associated primary ovarian insufficiency, and fragile X syndrome. Differences in the distribution and prevalence of CGG repeat length and of AGG interruption patterns have been reported among different populations and ethnicities. In this study we characterized the AGG interruption patterns within 3,065 normal CGG repeat alleles from nine world populations including Australia, Chile, United Arab Emirates, Guatemala, Indonesia, Italy, Mexico, Spain, and United States. Additionally, we compared these populations with those previously reported, and summarized the similarities and differences. We observed significant differences in AGG interruption patterns. Frequencies of longer alleles, longer uninterrupted CGG repeat segments and alleles with greater than 2 AGG interruptions varied between cohorts. The prevalence of fragile X syndrome and FMR1 associated disorders in various populations is thought to be affected by the total length of the CGG repeat and may also be influenced by the AGG distribution pattern. Thus, the results of this study may be important in considering the risk of fragile X-related conditions in various populations

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Length of uninterrupted CGG repeats determines instability in the FMR1 gene

Cited by 432 publications

References 33 publications

Intermediate FMR1 alleles and cognitive and/or behavioural phenotypes

Intermediate FMR1 alleles and cognitive and/or behavioural phenotypes

Fragile X full mutation expansions are inhibited by one or more AGG interruptions in premutation carriers

Distribution of AGG interruption patterns within nine world populations

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