Number Of CGG Repeats Research Articles

Reliable and Sensitive Detection of Fragile X (Expanded) Alleles in Clinical Prenatal DNA Samples with a Fast Turnaround Time

This study evaluated a large set of blinded, previously analyzed prenatal DNA samples with a novel, CGG triplet-repeat primed (TP)-PCR assay (Amplidex FMR1 PCR Kit; Asuragen, Austin, TX). This cohort of 67 fetal DNAs contained 18 full mutations (270 to 1100 repeats, including 1 mosaic), 12 premutations (59 to 150 repeats), 9 intermediate mutations (54 to 58 repeats), and 28 normal samples (17 to 50 repeats, including 3 homozygous female samples). TP-PCR accurately identified FMR1 genotypes, ranging from normal to full- mutation alleles, with a 100% specificity (95% CI, 85.0% to 100%) and a 97.4% sensitivity (95% CI, 84.9% to 99.9%) in comparison with Southern blot analysis results. Exact sizing was possible for a spectrum of normal, intermediate, and premutation (up to 150 repeats) alleles, but CGG repeat numbers >200 are only identified as full mutations. All homozygous alleles were correctly resolved. The assay is also able to reproducibly detect a 2.5% premutation and a 3% full-mutation mosaicism in a normal male background, but a large premutation in a full male mutation background was masked when the amount of the latter was >5%. Implementation of this TP-PCR will significantly reduce reflex testing using Southern blot analyses. Additional testing with methylation-informative techniques might still be needed for a few cases with (large) premutations or full mutations.

A Dual-Mode Single-Molecule Fluorescence Assay for the Detection of Expanded CGG Repeats in Fragile X Syndrome

Fragile X syndrome is the leading cause of inherited mental impairment and is associated with expansions of CGG repeats within the FMR1 gene. To detect expanded CGG repeats, we developed a dual-mode single-molecule fluorescence assay that allows acquisition of two parallel, independent measures of repeat number based on (1) the number of Cy3-labeled probes bound to the repeat region and (2) the physical length of the electric field-linearized repeat region, obtained from the relative position of a single Cy5 dye near the end of the repeat region. Using target strands derived from cell-line DNA with defined numbers of CGG repeats, we show that this assay can rapidly and simultaneously measure the repeats of a collection of individual sample strands within a single field of view. With a low occurrence of false positives, the assay differentiated normal CGG repeat lengths (CGG( N ), N = 23) and expanded CGG repeat lengths (CGG( N ), N = 118), representing a premutation disease state. Further, mixtures of these DNAs gave results that correlated with their relative populations. This strategy may be useful for identifying heterozygosity or for screening collections of individuals, and it is readily adaptable for screening other repeat disorders.

FMR1 Repeats and Ovarian Reserve: CGG Repeat Number does not Influence Antral Follicle Count

Background: Premature ovarian failure has been reported in women carrying FMR1 premutations. This study explored the association between number of FMR1 CGG repeats and Antral Follicle Count (AFC) in infertile women. Methods: Retrospective cross-sectional study; 350 infertile women underwent FMR1 genotyping and ultrasound for AFC at an academic reproductive medical center. Women with premature ovarian failure were excluded. FMR1 repeats were classified as Result(s): Only 1 woman carried a premutation, with 57 CGG repeats. Seven women carried intermediate alleles (<2%). FMR1 repeat number was not a significant predictor of AFC in an age-adjusted linear regression when the highest number allele or both allele members were included. Age-adjusted AFC did not differ between FMR1 groups by any of the classification systems used. Conclusion(s): FMR1 intermediate alleles and premutations are rare in infertile women in the San Francisco Bay Area, with prevalence comparable to the general population. FMR repeat number does not correlate with AFC in this ethnically diverse population.

Evaluation of the Human Fragile X Mental Retardation 1 Polymerase Chain Reaction Reagents to Amplify theFMR1Gene: Testing in a Clinical Diagnostic Laboratory

Fragile X syndrome (FXS) is caused by the absence of a functional fragile X mental retardation protein (FMRP). In most cases, the molecular mutation is an expansion and consequent methylation of the CGG trinucleotide repeat in the 5' end of the FMR1 gene. Polymerase chain reaction (PCR)-based assays that overcome the limitations of amplifying >100-150 CGG repeats have been designed. One such product, Human FMR1 PCR Reagents, can detect expanded mutation alleles without determining methylation status. We used this assay to amplify 70 clinical samples previously tested in three clinical laboratories, including 28 full mutation alleles, 17 premutation alleles, 6 gray zone alleles, and 21 normal samples (51 normal alleles including 5 homozygous females). The results were concordant with previously reported results. All full and premutation alleles were identifiable: repeat sizes are not assigned when the CGG repeat number is >200 and all full and premutation alleles were scored in the same category using this assay. All normal and gray zone alleles were within 0-1 repeat of their previously reported allele sizes. This method identified a mosaic premutation/full mutation pattern in 12/21 samples previously identified as full mutation only and in 5/7 samples previously reported as mosaic premutation/full mutation. These results demonstrate that this assay provides comparable results to the combination of PCR/Southern blot methodologies. Additional issues such as technologist time, reagent costs, turnaround times, and sample requirements are comparable to the PCR/Southern blotting assays currently utilized; however, methylation status cannot be determined using this assay. It is likely that PCR-only based assays will eventually replace previous methods for FXS and that Southern blotting or another methylation assay will only be utilized when determination of methylation status is necessary. This type of assay may also be utilized for other nucleotide expansion disorders.

Number of CGG repeats in the FMR1 gene of Japanese patients with primary ovarian insufficiency

To define the number of CGG repeats in the FMR1 gene of Japanese patients with primary ovarian insufficiency (POI) and normal controls. Retrospective, controlled cohort study. Outpatient department of an academic tertiary center. One hundred twenty-eight consecutive Japanese patients with sporadic, nonsyndromic POI and 98 controls with normal menstruation. Deoxyribonucleic acid was obtained from the plasma of each subject. Differences in the distribution of CGG repeat numbers between patients with POI and controls. Six alleles in the intermediate range and two in the premutation range were found in five and two patients with POI, respectively, but none were identified in normal controls. The prevalence of FMR1 premutation among Japanese POI patients was 1.56% (2 of 128). The prevalence of having >36 CGG repeats in the FMR1 gene was significantly higher in patients with POI than in controls, and age at the onset of amenorrhea was significantly lower in patients with >38 repeats. More than 36 CGG repeats in the FMR1 might intensify the etiology of POI, at least up to the premutation range.

Sleep apnea in fragile X premutation carriers with and without FXTAS

This report seeks to establish the prevalence of sleep apnea in patients with the fragile X mental retardation 1 (FMR1) premutation with and without fragile X-associated tremor/ataxia syndrome (FXTAS) and to determine any correlation between CGG repeat and FMR1 mRNA levels with sleep apnea prevalence. Demographic and medical data from 430 (229 males, 201 females) participants were used in this analysis. Participants included premutation carriers with (n = 118) and without FXTAS (n = 174) as well as controls without the premutation (n = 123). Logistic regression models were employed to estimate the odds ratio of sleep apnea relative to controls, adjusted for age and gender, and also to examine potential association with CGG size and FMR1 mRNA expression level. The observed proportion of sleep apnea in premutation carriers with and without FXTAS and controls are 31.4% (37/118), 8.6% (15/174), and 13.8% (17/123), respectively. The adjusted odds of sleep apnea for premutation carriers with FXTAS is about 3.4 times that compared to controls (odds ratio, OR = 3.4, 95% confidence interval (CI) 1.8-7.4; P = 0.001), and similarly relative to premutation carriers without FXTAS (OR = 2.9, 95% CI 1.2-6.9; P = 0.014). The risk of sleep apnea was not different between controls and premutation carriers without FXTAS. The presence of sleep apnea is not associated with CGG repeat numbers nor FMR1 mRNA expression level among premutation carriers. Our data supports a higher prevalence and risk of sleep apnea in patients with FXTAS. We recommend that all patients diagnosed with FXTAS be screened for sleep apnea given the negative and perhaps accelerative impact sleep apnea may have on their FXTAS progression.

The Role of AGG Interruptions in the Transcription of FMR1 Premutation Alleles

Fragile X associated disorders are caused by a premutation allele in the fragile X mental retardation 1 gene (FMR1) and are hypothesized to result from the toxic effect of elevated levels of expanded FMR1 transcripts. Increased levels of FMR1 mRNA have indeed been reported in premutation carriers; however the mechanism by which expanded alleles lead to elevated levels of FMR1 mRNA in premutation carriers is unknown. Within the CGG repeat tract AGG interruptions are found, generally 1–3 present in normal/intermediate alleles (6–54 CGG repeats) and usually 0–1 in premutation alleles (55–200 CGG repeats). They are present at specific locations, generally occurring after 9 or 10 uninterrupted CGG repeats [(CGG)9AGG(CGG)9AGG(CGG)n ]. We evaluated both the number of AGG interruptions and the resulting length of the uninterrupted 3′ CGG repeat pure tract in premutation alleles derived from two large cohorts of male and female carriers to determine whether the presence of AGG interruptions or the length of a pure stretch of CGG repeats influence the levels of FMR1 mRNA in blood. Our findings indicate that neither the number of AGG interruptions, nor their position along the CGG tract have a significant affect on mRNA levels in premutation carriers. We also, as expected based on previous findings, observed a highly significant correlation between CGG repeat number (as both total length and length of pure CGG stretch) and FMR1 mRNA expression levels, in both males and females. Importantly, we did not observe any significant difference in FMR1 mRNA levels in premutation carriers based on age.

Increased frequency of occult fragile X-associated primary ovarian insufficiency in infertile women with evidence of impaired ovarian function

The FMR1 premutation is associated with overt primary ovarian insufficiency (POI). However, its prevalence in women with occult POI (i.e. menstrual cycles, but impaired ovarian response) has not been examined. We hypothesized that both the FMR1 premutation and intermediate allele is more frequent in infertile women with occult POI than in controls, and that a repeat length cutoff might predict occult POI. All subjects were menstruating women <42 years old and with no family history of unexplained mental retardation, autism or fragile X syndrome. Cases had occult POI defined by elevated FSH or poor response to gonadotrophin therapy (n = 535). Control subjects (n = 521) had infertility from other causes or were oocyte donors. Prevalence of the FMR1 premutation and intermediate alleles was examined and allele length was compared between controls and women with occult POI. The frequency of the premutation (7/535 versus 1/521; P< 0.05) and intermediate alleles (17/535 versus 7/521; P< 0.05) was higher in women with occult POI than in controls. The allele with the greatest number of CGG repeats was longer in women with occult POI compared with controls (32.7 ± 7.1 versus 31.6 ± 4.3; P < 0.01). A receiver operating characteristic curve examining repeat length as a test for occult POI had an area of 0.56 ± 0.02 (P < 0.01). A repeat cutoff of 45 had a specificity of 98%, but a sensitivity of only 5% to identify occult POI. The positive predictive value was only 21% for a fertility population that has ∼ 22% of its patients with occult POI. The data suggest that FMR1 premutations and intermediate alleles are increased in women with occult POI. Thus, FMR1 testing should be performed in these women as some will have fragileX-associated POI. Although the FMR1 repeat lengths were longer in women with occult POI, the data do not support the use of a repeat length cutoff to predict occult POI.

Nucleosomal occupancy and CGG repeat expansion: a comparative analysis of triplet repeat region from mouse and human fragile X mental retardation gene 1

The expansion of CGG repeats in the 5'-untranslated region (5'UTR) of FMR1 gene is the molecular basis of fragile X syndrome in most of the patients. The nature of the flanking sequences in addition to the length and interruption pattern of repeats is predicted to influence CGG repeat instability in the FMR1 gene. We investigated nucleosome occupancy as a contributor to CGG repeat instability in a transgenic mouse model containing unstable (CGG)(26,) from human FMR1 cloned downstream of nucleosome-excluding sequence. We observe that the transgene has an open chromatin structure compared to the stable endogenous mouse Fmr1 within the same nucleus. CGG repeats in mouse Fmr1 are flanked by nucleosomes unlike the repeats in the transgene in all the tissues examined. Further in vitro chromatin reconstitution experiments show that DNA fragment without the SV40ori/EPR (nucleosome-excluding sequence) forms more stable chromatin than the one containing it, despite having the same number of CGG repeats. The correlation between nucleosomal organisation of the FMR1 gene and CGG repeat instability was supported by significantly lower frequency of repeat expansion in mice containing an identical transgene without the SV40ori/EPR. Our studies demonstrate that flanking DNA sequences can influence repeat instability through modulation of nucleosome occupancy in the region.

CGG-repeat length threshold for FMR1 RNA pathogenesis in a cellular model for FXTAS

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that affects carriers of premutation alleles (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. The presence of elevated levels of expanded mRNA found in premutation carriers is believed to be the basis for the pathogenesis in FXTAS, but the exact mechanisms by which the mRNA causes toxicity are not known. In particular, it is not clear whether there is a threshold for a CGG-repeat number below which no cellular dysregulation occurs, or whether toxicity depends on mRNA concentration. We have developed a doxycycline-inducible episomal system that allows us to study separately the effects of CGG-repeat number and mRNA concentration (at fixed CGG-repeat length) in neuroblastoma-derived SK cells. Our findings show that there is a CGG-repeat size threshold for toxicity that lies between 62 and 95 CGG repeats. Interestingly, for repeat sizes of 95 CGG and above, there is a clear negative correlation between mRNA concentration and cell viability. Taken together, our results provide evidence for an RNA-toxicity model with primary dependence on CGG-repeat size and secondary dependence on mRNA concentration, thus formally ruling out any simple titration model that operates in the absence of either protein-binding cooperativity or some form of length-dependent RNA structural transition.

A New Method for FMR1 Gene Methylation Screening by Multiplex Methylation-Specific Real-Time Polymerase Chain Reaction

Fragile X Syndrome (FXS) is the most common form of inherited mental retardation in men. It is caused by abnormalities in the FMR1 gene that are associated with CGG repeat expansion and the hypermethylation status of its promoter. Methylated alleles lead to transcriptional inhibition and consequent loss of Fragile X Mental Retardation Protein. Chemical modification of cytosine to uracil by bisulfite treatment has proved to be an attractive method for DNA methylation studies that precludes labor-intensive Southern blot analysis, which is the gold standard test for FXS. In this report, bisulfite-treated DNA samples were amplified using real-time multiplex methylation-specific polymerase chain reaction followed by melting curve analysis. Our results show that all control samples with known CGG repeat numbers and methylation statuses were correctly diagnosed. The samples from 43 male patients were also successfully diagnosed, which were in complete agreement with the results of Southern blotting. By such means, 39 patients were found to have an unmethylated allele; 3, a fully mutated allele; and 1, both methylated and unmethylated alleles, thus implying a diagnosis of mosaicism. In conclusion, we find our method to be convenient for screening a large number of male patients with FXS, because it is rapid and easy to perform, especially when there is a low quantity of DNA that must be sensitively and accurately assayed.

Prepulse inhibition in patients with fragile X-associated tremor ataxia syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late onset neurodegenerative disorder that affects carriers of the fragile X premutation, typically after age 50. Common symptoms include intention tremor, ataxia, neuropathy, autonomic dysfunction, cognitive decline, and dementia. The objectives of this study were to determine if patients with FXTAS have altered prepulse inhibition (PPI; a measure of sensorimotor gating), and to study possible correlations between PPI, molecular status, and cognitive performance. A passive acoustic PPI paradigm was applied in 163 subjects; 121 carriers of the fragile X premutation, and 42 healthy controls. There were significant differences in PPI between premutation carriers with FXTAS and controls at PPI 60 ms, and at 120 ms. This effect was more prominent in the male FXTAS patients. There was a tendency to an impaired PPI in female premutation carriers at the 120 ms condition. There was a significant correlation between the PPI deficit and a higher CGG repeat number. The results show an impairment in sensorimotor gating processes in male carriers of the fragile X premutation, which is more prominent in patients with FXTAS.

FMR1 trinucleotide repeat size is predictive of ovarian response

OBJECTIVE: Premature ovarian failure(POF) is prevalent in 13-26% of FMR1 premutation carriers. This risk appears to increase as trinucleotide size increases up to 99 repeats, after which the risk plateaus or decreases. We evaluated women who were intermediate risk or premutation carriers undergoing IVF to determine whether CGG repeat size correlates with ovarian response. DESIGN: Retrospective. MATERIALS AND METHODS: Patients undergoing IVF with fragile X DNA testing were identified. Based on the American College of Medical Genetics, patients with 41-54 repeats were classified as intermediate risk and those with 55-199 repeats as premutation carriers. Only patients with CGG repeats ≥41 were included for analysis. Correlation between FSH, peak E2, total GND dose, number of oocytes, fertilization and the number of CGG repeats was performed using Pearson's correlation. Additionally, comparison of cycle outcomes of intermediate risk and premutation carrier patients was carried out using ANOVA and chi-square. RESULTS: In total, 44 patients initiated 77 cycles. A significantly positive correlation was found between total GND dose and CGG repeats(p=0.0007; r=0.38). Although age was similar, FSH and total GNDs were significantly higher in the premutation group, accompanied by lower peak E2 levels.Tabled 1INTERMEDIATE RISK (n=52)PREMUTATION (n=25)PAge34.2 ± 4.834.0 ± 5.1.83FSH7.1 ± 3.210.2 ± 4.2.002*Peak E22098 ± 10051535 ± 1356.043*Total GND dose (IU)3248 ± 13804236 ± 2040.014*Cancellation7.2%40%.001*No. retrieved oocytes17.1 ± 10.314.9 ± 12.2.49Fertilization61%62.3%.77Clinical pregnancy25/46 (54.3%)4/15 (26.6%).12Implantation28.9%20%.41Loss4/25 (16%)0/4 (n/a).39 Open table in a new tab CONCLUSION: A positive correlation, extending to intermediate risk patients, was found between CGG repeat size and total GND dose. Trinucleotide size may be correlated with ovarian response, and evidence of ovarian dysfunction can be found in women with >54 repeats.

FMR1 repeats and ovarian function: comparing number of CGG repeats and antral follicle count

OBJECTIVE: Premature ovarian insufficiency has been reported in women carrying FMR1 premutations (Streuli 2009) We explored the association between number of FMR1 CGG repeats and antral follicle count (AFC) in infertile women.

PGD for fragile X syndrome: ovarian function is the main determinant of success

PGD for fragile X syndrome (FRAX) is inefficient, probably owing to fewer oocytes, poor embryo quality and difficulties in genetic analysis. We investigated IVF-PGD in FRAX mutation carriers compared with controls, looking at the effects of oocyte and embryo number/quality on live birth outcome. We performed IVF-PGD in 27 patients with the FRAX mutation and 33 controls with other genetic diseases. Genetic testing was by multiplex PCR. Seventy-nine and 108 IVF-PGD cycles were started in FRAX mutation carriers and controls, respectively. Twenty-two patients had a premutation (CGG repeat number 60-200) and five had a full mutation (300-2000 CGG repeats). FRAX patients required higher doses of gonadotrophins (6788 ± 2379 versus 4360 ± 2330, P< 0.001) but had lower peak serum estradiol levels (8166 ± 5880 versus 10 211 ± 4673, P = 0.03) and fewer oocytes retrieved (9.8 ± 6 versus 14 ± 8, P = 0.01). The cancellation rate (unsatisfactory ovarian response) was higher in the FRAX group than in the control group (13 versus 1%, P < 0.001). When embryos were transferred, ongoing pregnancy/live birth rates per transfer were similar (29 versus 36%, P = 0.54). Ovarian dysfunction in FRAX carriers is more prevalent and profound than previously appreciated, with a high cancelation rate and reduced efficiency of PGD. The main determinant for successful PGD for FRAX is ovarian dysfunction. When embryo transfer is possible, the results are comparable to PGD for other monogenic diseases.

X-chromosome terminal deletion in a female with premature ovarian failure: Haploinsufficiency of X-linked genes as a possible explanation

BackgroundPremature ovarian failure (POF) has repeatedly been associated to X-chromosome deletions. FMR1 gene premutation allele's carrier women have an increased risk for POF. We intent to determine the cause of POF in a 29 year old female, evaluating both of these situations.MethodsConcomitant analysis of FMR1 gene CGG repeat number and karyotype revealed an X-chromosome terminal deletion. Fluorescence in situ further characterized the breakpoint. A methylation assay for FMR1 gene allowed to determine its methylation status, and hence, the methylation status of the normal X-chromosome.ResultsWe report a POF patient with a 46,X,del(X)(q26) karyotype and with skewed X-chromosome inactivation of the structural abnormal X-chromosome.ConclusionsDespite the hemizygosity of FMR1 gene, the patient does not present Fragile X syndrome features, since the normal X-chromosome is not subject to methylation. The described deletion supports the hypothesis that haploinsufficiency of X-linked genes can be on the basis of POF, and special attention should be paid to X-linked genes in region Xq28 since they escape inactivation and might have a role in this disorder. A full clinical and cytogenetic characterization of all POF cases is important to highlight a pattern and help to understand which genes are crucial for normal ovarian development.

Manifestaciones neurológicas en el adulto con premutación X frágil

Introduction Fragile X syndrome is an inherited form of mental retardation. It results from an abnormally expanded number of trinucleotide CGG repeats. Some grandfathers of these children become forgetful, have frequent falls and other neurological problems. Researchers have found a connection between fragile X syndrome and the neurological symptoms in elderly men. This resulted in the recognition of a syndrome originally referred to as “intention tremor, parkinsonism and generalised brain atrophy in carriers of a fragile X premutation”. This premutation is also associated with premature ovarian failure. Methodology This paper reviews the literature on the neurological signs of fragile X premutation. Conclusions Fragile X premutation is a risk for movement disorders and cognitive dysfunction and it should be considered in patients with a family history of mental retardation or autism, and particularly in those females with premature ovarian failure.

A Novel FMR1 PCR Method for the Routine Detection of Low Abundance Expanded Alleles and Full Mutations in Fragile X Syndrome

Fragile X syndrome (FXS) is a trinucleotide-repeat disease caused by the expansion of CGG sequences in the 5' untranslated region of the FMR1 (fragile X mental retardation 1) gene. Molecular diagnoses of FXS and other emerging FMR1 disorders typically rely on 2 tests, PCR and Southern blotting; however, performance or throughput limitations of these methods currently constrain routine testing. We evaluated a novel FMR1 gene-specific PCR technology with DNA templates from 20 cell lines and 146 blinded clinical samples. The CGG repeat number was determined by fragment sizing of PCR amplicons with capillary electrophoresis, and results were compared with those for FMR1 Southern blotting analyses with the same samples. The FMR1 PCR accurately detected full-mutation alleles up to at least 1300 CGG repeats and consisting of >99% GC character. All categories of alleles detected by Southern blotting, including 66 samples with full mutations, were also identified by the FMR1 PCR for each of the 146 clinical samples. Because all full mutation alleles in samples from heterozygous females were detected by the PCR, allele zygosity was reconciled in every case. The PCR reagents also detected a 1% mass fraction of a 940-CGG allele in a background of 99% 23-CGG allele-a roughly 5- fold greater sensitivity than obtained with Southern blotting. The novel PCR technology can accurately categorize the spectrum of FMR1 alleles, including alleles previously considered too large to amplify; reproducibly detect low abundance full mutation alleles; and correctly infer homozygosity in female samples, thus greatly reducing the need for sample reflexing to Southern blotting.

The significance of the number of CGG repeats and autoantibodies in premature ovarian failure

The objective of this study was to determine whether there was a threshold for the number of CGG repeats in the FMR1 (fragile X) gene in premature ovarian ageing and premature ovarian failure and to investigate the association of this sequence with serum concentrations of anti-Müllerian hormone (AMH), inhibin B, anti-thyroid and anti-adrenal autoantibodies. In this prospective randomized controlled preliminary study, the number of triple CGG repeats and serum concentrations of FSH, AMH and aforementioned autoantibodies were evaluated in 79 women who were younger than 40 years old. FSH concentrations were between 12 and 50 IU/ml (premature ovarian ageing) in 30 women and were higher than 50 IU/ml (premature ovarian failure) in nine women; FSH concentrations were normal in 40 women. All women whose FSH concentrations were higher than 12 IU/ml had CGG repeats greater than 30. No women whose FSH concentrations were normal had a repeat number above 30. There was no significant relationship between the levels of antibodies and either CGG repeat numbers or FSH concentrations. In conclusion, the number of CGG repeats between 30 and 40 might be used to predict premature ovarian ageing and premature ovarian failure in infertile women.

Effects of race/ethnicity on triple CGG counts in the FMR1 gene in infertile women and egg donors

This cross-sectional cohort study investigated 385 females (344 infertile women and 41 oocyte donors), the numbers of CGG repeats on the FMR1 gene and differences between races/ethnicities. Traditional definitions of neuropsychiatric risks are classified as common, intermediate, premutation and full mutation ranges. Normal CGG count range was here, however, defined by box and whisker plot as 26-32 repeats (median 30). Distribution of abnormal outliers in CGG counts from this normal range was then compared between women of Caucasian, African and Asian descent. African and Asian women demonstrated a higher prevalence of two normal count alleles (65%) than Caucasians (54.3%; P=0.03). Caucasians demonstrated the highest rate of allele abnormalities (43.3%) and were the only race/ethnicity also demonstrating abnormalities in both FMR1 alleles. Asian women demonstrated significantly fewer low outlier counts than Caucasians (P=0.002) and Africans (P=0.03). This study, thus, suggests significant racial/ethnic differences in triple CGG counts on the FMR1 gene between races/ethnicities. Since CGG counts on FMR1 are associated with ovarian reserve, these findings may reflect potential differences between races/ethnicities in ovarian function and female fertility reported in the literature.