• Journal of Life Science
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• v.9 no.6
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• pp.704-708
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• 1999

This research was carried out for evaluating diagnostic value of antibody test in Fragile X syndrome. In antibody test of control individuals and carriers with a premutation, FMRP were detected in the lymphocytes, whereas the lymphocytes of male Fragile X syndrome patients were devoid of FMRP. Five Fragile X syndrome male patient, two Fragile X syndrome female patients, three carriers were diagnosed by southern blot. Five boys who were diagnosed as the patients by antibody test were turned out full mutation and having multiple smear beside normal single band. However, fragile site of X chromosome was not expressed in Fragile X syndrome patients by chromosome analysis. These results showed that antibody test was a fast and simple method, but the diagnostic power was "perpect" for males, whereas the results were less specific for females.r females.

• Journal of Genetic Medicine
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• v.2 no.2
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• pp.83-86
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• 1998

Though Fragile X syndrome is one of the most common inherited causes of mental retardation, it is not much detected yet in Korean population. One of the reason may be that the syndrome is not well known to the special education teachers as well as to the clinicians in this country. Thus, molecular test was undertaken to screen out fragile X syndrome in 122 children of two Korean schools for emotionally severely handicapped children. The subjects were all boys, previously known as having pervasive developmental disorder with or without mental retardation. Southern blot analysis of peripheral blood showed the abnormally enlarged (CGG)n repeat sequence associated with fragile X syndrome in two children. This finding suggests that the DNA testing for fragile X syndrome is warranted for Korean high risk population and that more concern about this syndrome is needed for the professionals who work for mentally handicapped children. The issues involved in genetic counseling for fragile X syndrome are discussed.

• Journal of Life Science
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• v.9 no.6
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• pp.639-645
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• 1999

This research was for investigating the physiological effect caused by genetic disorder and others. Serum protein, serum LDH, and serum CPK were analyzed on Fragile X syndrome patients, carriers, unclassified mental retardees, and Down's syndrome patients by cellulose acetate plate electrophoresis. Also enzyme activity of LDH and CPK were measured. Significant differences were observed between normal group and mental retardees in compositions of serum protein, serum LDH, serum CPK, and enzyme activities. Mean percentages of albumin were 53.70$\pm$7.73% for Fragile X syndrome patients, 57.09$\pm$7.73% for carriers, 47.33$\pm$6.06% for unclassified mental retardees, 50.19$\pm$ 15.72% for Down's syndrome patients. Mean percentages of ${\gamma}$-globulin were 19.64$\pm$6.71% for Fragile X syndrome patients, 19.24$\pm$3.38% for carries, 25.66$\pm$4.74 for unclassified mental retardees, 23.41$\pm$6.08% for Down's syndrome patients. Mean percentages of LDH3 were 27.76$\pm$2.72% for Fragile X syndrome patients, 22.70$\pm$2.76% for carriers, 25.42$\pm$1.26% for unclassified mental retardees, 27.72$\pm$2.58% for Down's syndrome patients. Mean percentages of LDH4 were 2.70$\pm$2.04 for Fragile X syndrome patients, 3.79$\pm$2.74% for carriers, so both of them were significantly lower than normal(P<0.05). Mean percentages of CK-MB were 3.96$\pm$5.56% for Fragile X syndrome patients, 8.80$\pm$7.92%. Mean percentages of CK-MM were 95.81$\pm$5.50% for Fragile X syndrome patients, 91.20$\pm$7.92% for carriers. These results showed that significant abnormal compositions of blood proteins might be caused by genetic disorder. However, further analysis of many patients will be needed for clear conclusion.

• Biomedical Science Letters
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• v.2 no.1
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• pp.127-132
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• 1996

The karyotype and the concentration of serum protein were investigated in Korean unclassified mental retardees. The results were as follows. Fragile X chromosomes were identified in three patients, and the frequencies of fragile X chromosome were 4~15%. The concentration of serum protein was 5.73$\pm$0.89(g/dl), and the A/G ratio was 0.86$\pm$0.14 in fragile X syndrome patients. The concentration of serum protein was 6.83 $\pm$0.72(g/dl), and the A/G ratio was 0.87$\pm$0.17 unclassified mental retardees. The results revealed that the level of globulin concentration and A/G ratio in fragile X syndrome patients and unclassified mental retardees were lower than in normal group and Down's patients.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.3 no.1
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• pp.147-157
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• 1992

The fragile X syndrome, which is considered to be synonymous with the Martin-Bell syndrome, is a relatively common form of X-linked mental retardation. The syndrome seems to occure in many different ethnic groups and its prevalence among mentally retarded males has been estimated to be in the order of 2 to 6%. The karyotypic hallmark of the syndrome is made up with a pronounced constriction near each tip of the long arm of the X chromosome(fragile site), shown in vitro only under conditions in which thymidylate production is blocked(lowered folate levels). Special culture media are needed to demonstrate this constriction site. Major clinical features associated with the syndrome include macroorchidism, large or prominent ears, significant emotional and behavioral dysfunctions such as hyperactivity, self-injury, lack of eye contact and social interaction, schizophrenia, autism, etc., and speech and language dysfunctions ranging from nonverbal to verbal speech with moderate to severe expressive language delays. Some have minor clinical features in common such as an increase in birth weight high forehead, prognathism, increased head circumference in infancy and childhood which did not persist into adult life. The recent research findings have shown that the fragile X syndrome is associated with infantile autism. Many patients with the fragile X syndrome fulfill the diagnostic criteria for infantile autism. Therefore it is recommendable that any patient with developmental delays and autism or autistic manifestations should have a chromosomal analysis, including fragile X examination. In the present review, historical aspects, incidence, and clinical features are presented. Recent anecdotal reports of the association with autism and the clinical improvement following high dose folic acid treatment will be discussed.

• Journal of Genetic Medicine
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• v.5 no.1
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• pp.41-46
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• 2008

Purpose : Fragile X syndrome (FXS) is the most common heritable cause of cognitive impairment. FXS is caused by hyperexpansion and hypermethylation of a polymorphic CGG trinucleotide repeat in the 5' untranslated region of the fragile X mental retadation-1(FMR1) gene. Combination of Southern blotting and simple polymerase chain reaction(PCR) amplification of the FMR1 repeat region is commonly used for diagnosis in females. To give a definite diagnosis in a female child suspected of having FXS, we carried out the molecular diagnostic test for FXS using the recently developed Abbott Molecular Fragile X PCR Kit. Methods : The PCR amplification of the FMR1 repeat region was performed using the Abbott Mdecular Fragile X PCR Kit. The amplified products were analyzed by size-separate analysis on 1.5% agarose gels and by DNA fragment analysis using Gene scan. Results : Agarose gel and Gene scan analyses of PCR products of the FMR1 repeat region showed that the patient had two heterozygous alleles with a normal 30 repeats and full mutation of >200 repeats whereas her mother had two heterozygous alleles with the normal 30 repeats and premutation of 108 repeats, suggesting that the premutation of 108 repeats in her mother may have led to the full mutation of >200 repeats in the patient. Conclusion : We diagnosed FXS in a female patient using a simplified molecular diagnostic test. This commercially available diagnostic test for FXS, based on PCR, may be a suitable alternative or complement method to Southern blot analysis and PCR analysis and/or methylation specific(MS)-PCR analysis for the molecular diagnosis of FXS in both males and females.

• Molecules and Cells
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• v.28 no.6
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• pp.501-507
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• 2009

Fragile X syndrome (FXS) is caused by a lack of the fragile X mental retardation protein (FMRP) due to silencing of the Fmr1 gene. As an RNA binding protein, FMRP is thought to contribute to synaptic plasticity by regulating plasticity-related protein synthesis and other signaling pathways. Previous studies have mostly focused on the roles of FMRP within the hippocampus - a key structure for spatial memory. However, recent studies indicate that FMRP may have a more general contribution to brain functions, including synaptic plasticity and modulation within the prefrontal cortex. In this brief review, we will focus on recent studies reported in the prefrontal cortex, including the anterior cingulate cortex (ACC). We hypothesize that alterations in ACC-related plasticity and synaptic modulation may contribute to various forms of cognitive deficits associated with FXS.

• Journal of Genetic Medicine
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• v.9 no.2
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• pp.73-77
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• 2012

Purpose: Fragile X carrier detection before or at early pregnancy through a wide screening program may not only confer a risk of having offspring with Fragile X syndrome (FXS), but may also confer a risk for Fragile X-associated primary ovarian insufficiency and Fragile X-associated tremor/ataxia syndrome. However, prior to the implementation of such a program, the carrier prevalence in a population and the availability of effective screening test should be evaluated. The aim of our study was to determine the prevalence of premutation carriers and to evaluate the feasibility of screening test. Materials and Methods: The blood samples were obtained from 8,641 pregnant women with no family history of mental retardation. We performed a three-primer CGG repeat primed (RP) PCR using the AmplideX$^{TM}$ FMR1 PCR kit (Asuragen, Inc. Austin, TX, USA). Samples showing full mutation alleles were reflexed to Southern blot analysis for methylation status and sizing. Results: Among the 8,641 women, we found 8 premutation carriers (1:1,090, 0.09%) and 46 women with an intermediate allele (1:190, 0.53%). No woman was found to carry the fully mutated allele. All the detected alleles were within the CGG repeat range of 8-117. Among the 8,641 samples, 29 and 30 CGG repeats represent 66.6% of all cases. The CGG RP PCR method provides robust detection of expanded alleles and resolves allele zygosity, thus minimizing the number of samples that require Southern blot analysis. Conclusion: This is the first study that has focused on the prevalence of FXS premutation carriers and FMR1 allele distribution in normal pregnant women. These data have important implications for population-based fragile X carrier screening in Korea.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.11 no.1
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• pp.3-15
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• 2000

Objectives：There has been a rapid expansion of studies aimed at elucidating the genetic basis of autistic disorder, especially it’ relationship to fragile-X syndrome. The detection of fragile X chromosome(Xq27.3) by cytogenetic analysis has revealed many difficulties in testing. Therefore, to explore the relationship between autistic disorder and fragile X syndrome, this study administered molecular biologic methods which examined an unstable CGG repeat within the fragile X mental retardation-1(FMR-1) gene. Methods：Ninety nine autistic children and eight normal control children were tested. The number of CGG repeats within FMR-1 gene was measured after amplification by PCR, and cytogenetic analysis was also carried out to detect fragile site Xq27.3. Southern blot hybridization, using StB12.3 and/or Pfxa3 probe, was done for the patients showing expansion of more than 50 CGG repeats (premutation). Results：All but two autistic patients had no expansion in CGG repeats by PCR and there was no significant statistical difference in number of CGG repeat in comparison with normal control. Two autistic patients, considered as premutation by PCR analysis, had no full mutation or premutation by Southern blot hybridization. All autistic children tested did not have any abnormal karyotype or fragile site Xq27.3. Conclusions：These results suggest that autistic patients may not have abnormality in FMR-1 gene or abnormal expansion in CGG repeat. In conclusion, fragile X syndrome may not be antecedent of autistic disorder.

• BMB Reports
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• v.39 no.6
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• pp.766-773
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• 2006

Fragile-X-syndrome (FXS) is the most common type of inherited cognitive impairment. The underlying molecular alteration consists of a CGG-repeat amplification within the FMR-1 gene. The phenotype is only apparent once a threshold in the number of repeats has been exceeded (full mutation). The aim of this study was to characterize the FMR-1 CGG-repeat status in Argentine patients exhibiting mental retardation. A total of 330 blood samples from patients were analyzed by PCR and Southern blot analysis. Initially, DNA from 78 affected individuals were studied by PCR. Since this method is unable to detect high molecular weight alleles, however, we undertook a second approach using the Southern blotting technique to analyze the CGG repeat number and methylation status. Southern blot analysis showed an altered pattern in 14 out of 240 (6%) unrelated patients, with half of them presenting a mosaic pattern. Eight out of 17 families (47%) showed a (suggest deleting highlight). The characteristic FXS pattern was identified in 8/17 families (47%), and in 4 of these families 25% of the individuals presented with a mosaic model. The expansion from pre-mutation to full mutation was shown to occur both at the pre and post zygotic levels. The detection of FXS mutations has allowed us to offer more informed genetic counseling, prenatal diagnosis and reliable patient follow-up.