FRAXA and FRAXE prevalence in patients with nonspecific mental retardation in the Hellenic population

Syrrou, Maria; Georgiou, Ioannis; Grigoriadou, Maria; Petersen, Michael B.; Kitsiou, Sofia; Pagoulatos, Gerassimos N.; Patsalis, Philippos C.

doi:10.1002/(sici)1098-2272(1998)15:1<103::aid-gepi8>3.0.co;2-8

Cited by 14 publications

(4 citation statements)

References 27 publications

(15 reference statements)

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“…1). Thus, prevalence of FXS full mutation in this high-risk population from Central Java, Indonesia, is 4.0% (1.1% in males and 7.1% in females; 95% confidence interval (2.0%, 8.1%) in agreement with reports from previous studies in other populations) (Sutherland, 1985;Syrrou et al, 1998;de Vries et al, 1999;Faradz et al, 1999;Pouya et al, 2009). However, the FXS full mutation was 0.72% (1/139) in the ID populations alone.…”

Section: Resultssupporting

confidence: 90%

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Identification of Expanded Alleles of theFMR1Gene Among High-Risk Population in Indonesia by Using Blood Spot Screening

Winarni

Utari

Mundhofir

et al. 2012

Genetic Testing and Molecular Biomarkers

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The prevalence of Fragile X Syndrome (FXS) is 1 in 4000 in males and 1 in 2500 in males and females, respectively, in the general population. Several screening studies aimed at determining the prevalence of FXS have been conducted in individuals with intellectual disabilities (IDs) with a prevalence varying from 1.15% to 6.3% across different ethnic groups. A previous study in Indonesia showed an FXS prevalence of 1.9% among the ID population. A rapid, effective, and inexpensive method for FMR1 screening, using dried blood spots capable of detecting an expanded FMR1 allele in both males and females, was recently reported. We used this approach to screen 176 blood spots, collected from Central Java, Indonesia, for the presence of expanded FMR1 gene alleles. Samples were collected from high-risk populations: 112 individuals with ID, 32 obtained from individuals with diagnosis of autism spectrum disorders, and 32 individuals with a known family history of FXS. Fourteen subjects carrying an FMR1 expanded allele were identified including 7 premutations (55-200 CGG repeats) and 7 full mutations ( > 200 repeats). Of the seven subjects identified with a full mutation, one subject was from a nonfragile X family, and six from were families with a history of FXS.Introduction F ragile X syndrome (FXS), with a prevalence of 1:2500 to 1:4000 in the general population (Turner et al., 1996;Crawford et al., 2002;Hagerman, 2008), is the most common genetic cause of intellectual disability (ID) and the leading genetic cause of autism. Although prevalence estimates vary across studies, there is agreement that the risk of autism spectrum disorders (ASD) is higher in FXS than in many other neuro-developmental disorders. From recent studies, *2% to 6% of children with ASD have FXS (Li et al., 1993;Wassink et al., 2001;Estecio et al., 2002;Hagerman, 2002;Reddy, 2005), and *30% of children with FXS have ASD (see Appendix in Rogers et al., 2001;Kaufmann et al., 2004); Pervasive Developmental Disorder-Not Otherwise Specified is seen in an additional 30% (Harris et al., 2008). In fact, FXS is characterized by a broad spectrum of behavioral and emotional impairment, psychological problems, and learning disabilities in those without mental retardation or ID. In addition, specific physical features such as long face, macrognathia, prominent ears, hyperextensible joints, flat feet, and macroorchidism in puberty are observed (Hagerman et al., 1991;Lachiewicz and Dawson, 1994;Giangreco et al., 1996). The milder phenotypes are not accounted for in the current prevalence figures (Tassone et al., 1999;Hagerman, 2006). In addition, significant phenotypic involvement has emerged in some individuals with the premutation (55-200 CGG repeats), including fragile X-associated premature ovarian insufficiency (FXPOI) in females, and fragile X-associated tremor/ataxia syndrome (FXTAS) in both male and female aging carriers Sullivan et al., 2005). Prevalence for premutation alleles was *1 in 110-250 for females and 1 in 250-800 for males (Rousseau et al., 199...

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Section: Resultssupporting

confidence: 90%

“…A number of studies have been carried out in populations of individuals with IDs, with a prevalence varying from *1% to 6.3% (Sutherland, 1985;Syrrou et al, 1998;de Vries et al, 1999;Faradz et al, 1999;Pouya et al, 2009). A previous study in Indonesia showed an FXS prevalence of 1.9% among the ID population (Faradz et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Identification of Expanded Alleles of theFMR1Gene Among High-Risk Population in Indonesia by Using Blood Spot Screening

Winarni

Utari

Mundhofir

et al. 2012

Genetic Testing and Molecular Biomarkers

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“…Employing the DNA diagnostic methods, another report from Southern India revealed a frequency of 7%, comparable to our results [Baskaran et al, 1998]. However, we cannot compare our results with those reported for most other Western institutionalized populations, which included all unexplained MR cases in their study samples [Meadows et al, 1996;Mila et al, 1997;Elbaz et al, 1998;Syrrou et al, 1998;Crawford et al, 1999;Pang et al, 1999;Patsalis et al, 1999]. Considering the stringent selection criteria employed in this study, the overall frequency of FXS in India may be very similar to that reported for other Western and Asian populations [Patsalis et al, 1999].…”

Section: Discussionsupporting

confidence: 84%

Expansion mutation frequency and CGG/GCC repeat polymorphism inFMR1 andFMR2 genes in an Indian population

2000

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Based on molecular screening, we estimated the frequencies of fragile X syndrome and FRAXE syndrome in an institutionalized population (n = 130) in New Delhi, India. Eligibility criteria for inclusion of subjects in the study were mild/moderate mental retardation, with/without family history, and the fragile X clinical phenotype. Screening by Southern hybridization revealed an overall frequency of 0.077 of the syndrome in the sample population. The disorder was observed with a high frequency (0.1) among males as compared to females (0.027). No expansions of FMR2 allele were observed in the same study sample. CGG/GCC allelic polymorphism of FMR1 and FMR2 were established from a total of 392 X chromosomes, using the radioactive polymerase chain reaction–polyacrylamide gel electrophoresis method. Distinct repeat sizes, repeat ranges, and repeat modes characterised the FMR1 and FMR2 alleles. In the X chromosomes of both MR individuals and unaffected controls, unimodal values of 29 and 15 repeats in FMR1 and FMR2 genes, respectively, were observed. Allele frequency distribution was symmetrical at the FMR1 locus whereas a significant positive skew was observed for the FMR2 alleles. The observed heterozygosity of the FMR1 gene was 0.772 compared to 0.839 of FMR2. Correlation of CGG/GCC repeats of FMR1 and FMR2 did not show any association of repeat sizes at these two loci (correlation coefficient, ρ = 0.09). CGG/GCC repeat variation at FMR1 and FMR2 loci observed in this study sample are different from that reported for the other Caucasian and Asian populations. Genet. Epidemiol. 20:129–144, 2001. © 2001 Wiley‐Liss, Inc.

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“…In the majority of patients with FRAXA, full mutations have been reported in the literature among patients with mild to moderate mental retardation (Jacobs et al, 1993;Wang et al, 1993;Hofstee et al, 1994;Buttler et al, 1995;De Vries et al, 1997 salis et al, 1997;Baskaran et al, 1998;Syrrou et al, 1998). A recent review points out that only 3% of FRAXA patients were among the moderate to severe mental retardation group (Knight et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

FRAXA Screening in Brazilian Institutionalized Individuals with Nonspecific Severe Mental Retardation

Mulatinho

Llerena²,

Pimentel³

2000

Genetic Testing

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Individuals with mental disabilities are a heterogeneous group, mainly when we consider the etiology of mental retardation (MR). Recent advances in molecular genetics techniques have enabled us to unveil more about the molecular basis of several genetic syndromes associated with MR. In this study, we surveyed 85 institutionalized individuals with severe MR, 38 males and 47 females, by two molecular techniques, to detect CGG amplifications in the FMR1 gene. No FRAXA mutations were found in the FMR1 gene, reinforcing the low prevalence of Fragile X syndrome among institutionalized individuals with severe MR. We considered the PCR protocol used adequate for screening males with mental retardation of unknown etiology. The use of the Southern blot is still necessary for the decisive diagnosis of the Fragile X syndrome. To exclude chromosomal abnormalities associated with MR as a possible cause of the phenotype in these individuals, G-banded chromosome analysis was performed in all patients and 7.3% of chromosomal aberrations were found. Our results are similar to those reported previously and point to the necessity of expanding the molecular investigation toward other causes of MR, such as subtle chromosomal rearrangements, as suggested recent by a combination of fluorescence in situ hybridization (FISH) and PCR studies.

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FRAXA and FRAXE prevalence in patients with nonspecific mental retardation in the Hellenic population

Cited by 14 publications

References 27 publications

Identification of Expanded Alleles of theFMR1Gene Among High-Risk Population in Indonesia by Using Blood Spot Screening

Identification of Expanded Alleles of theFMR1Gene Among High-Risk Population in Indonesia by Using Blood Spot Screening

Expansion mutation frequency and CGG/GCC repeat polymorphism inFMR1 andFMR2 genes in an Indian population

FRAXA Screening in Brazilian Institutionalized Individuals with Nonspecific Severe Mental Retardation

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