Fragile X Syndrome: The FMR1 CGG Repeat Distribution Among World Populations

Peprah, Emmanuel

doi:10.1111/j.1469-1809.2011.00694.x

Cited by 80 publications

(75 citation statements)

References 152 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The CGG repeat sizes of 29 and 30 were found to be most common in all ethnic groups, together accounting for 61.1% of the alleles in the cohort and comparable with populations of western European ancestry and other populations in Asia, Indonesia, Brazil, Chile, Cameroon, Ghana and India, and in African Americans. [20] In the present study the 30 CGG repeat (found in 34% of cases) was the most common allele in the white population, which corroborates well with the 39% frequency reported by Goldman. [11] The most common allele in the black population in this study was shown to be 29 CGG repeats (in 41% of the total black cohort).…”

Section: Distribution Of Fmr-1 Allelessupporting

confidence: 81%

Diagnostic, carrier and prenatal genetic testing for fragile X syndrome and other FMR-1-related disorders in Johannesburg, South Africa: A 20-year review

Essop

Krause

2013

S Afr Med J

View full text Add to dashboard Cite

Background. 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. Objectives. To review, retrospectively, the genetic services for FXS and other FMR-1-related disorders -including fragile X-associated tremor/ataxia syndrome (FXTAS) and FMR-1-related primary ovarian insufficiency (POI) -at the Division of Human Genetics, Johannesburg, for diagnostic, carrier and prenatal genetic testing. Methods. The records of 2 690 patients who had genetic testing for FMR-1 between 1992 and 2012 were reviewed. Of these, 2 239 had diagnostic testing, 430 carrier or cascade testing and 17 prenatal testing for FXS. Four had FXTAS or POI testing. Polymerase chain reaction (PCR) and/or Southern blotting techniques were used to test the patients' samples for FMR-1 and FMR-2 expansions. Results. 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. In 17 prenatal tests, eight fetuses tested positive for FXS. 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. Conclusion. The findings support the presence of FXS, as the most common cause of ID, in all local populations. The FMR-1 CGG repeat distribution varied from that found in other studies. The number of family members tested was relatively low suggesting that many at-risk individuals are not being referred.

show abstract

Section: Distribution Of Fmr-1 Allelessupporting

confidence: 81%

Diagnostic, carrier and prenatal genetic testing for fragile X syndrome and other FMR-1-related disorders in Johannesburg, South Africa: A 20-year review

Essop

Krause

2013

S Afr Med J

View full text Add to dashboard Cite

show abstract

“…8 The present study was aimed at comparing the distribution of FMR1 genotypes between BRCA mutation carriers and non-carriers in a cohort of Italian women, free of cancer or affected by breast and/ or ovarian cancer, who were tested for the presence of BRCA mutation in a clinical setting because of their personal and/or familial cancer history.…”

Section: Introductionmentioning

confidence: 99%

The FMR1 CGG repeat test is not a candidate prescreening tool for identifying women with a high probability of being carriers of BRCA mutations

et al. 2013

View full text Add to dashboard Cite

The identification of women with a high probability of being carriers of pathogenic BRCA mutation is not straightforward and a major improvement would be the availability of markers of mutations that could be directly evaluated in individuals asking for genetic testing. The FMR1 gene testing was recently proposed as a candidate prescreening tool because an association between BRCA pathogenic mutations and FMR1 genotypes with 'low alleles' (CGG repeat number o26) was observed. To confirm this hypothesis, we evaluated the distribution of FMR1 alleles and genotypes between BRCA mutation carriers and non-carriers in a cohort of 147 Italian women, free of cancer or affected by breast and/or ovarian cancer, who were tested for the presence of BRCA mutation in a clinical setting. The distribution of FMR1 CGG repeat numbers in the two groups was similar (lower allele median/mean were 30/27.4 and 30/27.9, respectively; Mann-Whitney test P ¼ 0.997) and no difference in the FMR1 genotype distribution was present (v 2 ¼ 0.503, d.f. ¼ 2, P ¼ 0.78). This result is in contrast with literature data and suggests that FMR1 genetic testing is not a candidate BRCA prescreening tool. European Journal of Human Genetics (2014) 22, 280-282; doi:10.1038/ejhg.2013 published online 25 September 2013 Keywords: FMR1; BRCA; HBOC; mutation screening INTRODUCTIONThe decision to offer testing for BRCA mutations is challenging in many women in whom an inherited predisposition to breast/ovarian cancer is suspected, because of the associated costs, but also for the difficult interpretation of test results when genetic variants of uncertain significance are detected. Although several tools have been developed to help in this decision, their performance is unsatisfactory. 1 A major improvement would be the availability of markers of pathogenic BRCA mutations that could be directly evaluated in individuals candidate to (or asking for) genetic testing.A low ovarian response rate was observed in BRCA1 mutationpositive women with breast cancer undergoing in vitro fertilization, suggesting an association between BRCA1 mutation and occult primary ovarian insufficiency. 2 Impairment of functional ovarian reserve is associated with another genetic trait, the polymorphic CGG repeat of the Fragile X Mental Retardation 1 (FMR1) gene. 3 Female FMR1 premutation carriers (55-200 CGG repeats) are at increased risk of primary ovarian insufficiency (FXPOI). However, an increased risk of ovarian insufficiency was also reported in women with CGG repeat numbers still within the conventional normal range (o55 CGG repeats) but lower (o26 CGG repeats) or higher (35-55 CGG repeats) of the range of CGG repeats associated with normal folliculogenesis (26-34 CGG repeats). [4][5][6] Recently, Weghofer et al 7 have investigated whether BRCA mutations and FMR1 ovarian genotypes are interdependent: in Austrian women carrying a BRCA mutation they observed almost exclusively the presence of genotypes containing at least one FMR1 allele with a CGG repeat number below 26 (so calle...

show abstract

“…While the distribution of CGG repeat total length has been reported in a number of populations (27), fewer studies have reported the distribution of AGG interruptions within populations. This study reports on the AGG interruption patterns in a total of 3,065 normal alleles (9-40 CGG repeats) from 1,989 participants (males: n = 794; females: n = 1,195) from 9 countries: Australia, Chile, Emirates, Guatemala, Indonesia, Italy, Mexico, Spain, and USA.…”

Section: Introductionmentioning

confidence: 99%

Distribution of AGG interruption patterns within nine world populations

Yrigollen

Sweha

Durbin‐Johnson

et al. 2014

IRDR

View full text Add to dashboard Cite

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

show abstract

Fragile X Syndrome: The FMR1 CGG Repeat Distribution Among World Populations

Cited by 80 publications

References 152 publications

Diagnostic, carrier and prenatal genetic testing for fragile X syndrome and other FMR-1-related disorders in Johannesburg, South Africa: A 20-year review

Diagnostic, carrier and prenatal genetic testing for fragile X syndrome and other FMR-1-related disorders in Johannesburg, South Africa: A 20-year review

The FMR1 CGG repeat test is not a candidate prescreening tool for identifying women with a high probability of being carriers of BRCA mutations

Distribution of AGG interruption patterns within nine world populations

Contact Info

Product

Resources

About