scholarly journals Simple molecular diagnostic method for fragile X syndrome in Egyptian patients: pilot study.

2014 ◽  
Vol 61 (2) ◽  
Author(s):  
Nagwa A Meguid ◽  
Manal F Ismail ◽  
Rasha S El-Mahdy ◽  
Maged A Barakat ◽  
Mostafa K El-Awady
Keyword(s):  
Mental Retardation ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Clinical Manifestations ◽  
Recessive Gene ◽  
Molecular Diagnostic ◽  
Major Barrier ◽  
Cgg Repeats ◽  
Egyptian Patients ◽  
Pcr Method

Poor knowledge about Fragile X syndrome (FXS) may be a major barrier to early diagnosis that could improve quality of life and prognosis especially in the developing countries. The aim of this study was to evaluate simple and reproducible method for premutation detection in females of fragile X families for the first time in Egypt. We have developed a rapid modified polymerase chain reaction (PCR)-based screening tool for expanded Fragile X mental retardation 1 (FMR1) alleles. This method utilizes betaine as additive to facilitate FMR 1 gene amplification. We screened fifty three males, thirty two first-degree females; twenty normal healthy controls in addition to six reference samples. Simple PCR method showed 16 males with abnormal CGG repeats, where 10 of their mothers and four sisters had FMR 1 premutation. Consanguineous marriage was present in 66.6% percent of the studied families. Studying the correlation between genotype and clinical manifestations showed premature ovarian failure in 40% and learning disability in 50% of the studied female carriers. FXS has to be ruled out in families with consanguineous parents, before assuming that familial mental retardation is due to autosomal recessive gene defects. Early carrier detection may reduce the number of affected children. In conclusion, more studies are still needed of much larger sample size with known allele sizes in order to guarantee the accuracy of the method used.

scholarly journals Simplified Molecular Diagnosis of Fragile X Syndrome by Fluorescent Methylation-Specific PCR and GeneScan Analysis

2006 ◽  
Vol 52 (8) ◽  
pp. 1492-1500 ◽  
Author(s):  
Youyou Zhou ◽  
Josephine MS Lum ◽  
Gare-Hoon Yeo ◽  
Jennifer Kiing ◽  
Stacey KH Tay ◽  
...  
Keyword(s):  
Fragile X Syndrome ◽  
Southern Blot ◽  
Molecular Diagnosis ◽  
Blot Analysis ◽  
Southern Blot Analysis ◽  
Fragile X ◽  
Molecular Diagnostic ◽  
Methylation Specific Pcr ◽  
Specific Pcr ◽  
Cgg Repeats

Abstract Background: Fragile X syndrome (FXS), the most common cause of inherited mental impairment, is most commonly related to hyperexpansion and hypermethylation of a polymorphic CGG trinucleotide repeat in the 5′ untranslated region of the FMR1 gene. Southern blot analysis is the most commonly used method for molecular diagnosis of FXS. We describe a simplified strategy based on fluorescent methylation-specific PCR (ms-PCR) and GeneScan™ analysis for molecular diagnosis of fragile X syndrome. Methods: We used sodium bisulfite treatment to selectively modify genomic DNA from fragile X and normal lymphoblastoid cell lines and from patients. We then performed ms-PCR amplification using fluorescently-labeled primers complementary to modified methylated or unmethylated DNA. Amplification products were resolved by capillary electrophoresis. FMR1 mutational status was determined by a combination of fluorescent peak sizes and patterns on the GeneScan electropherogram. Results: DNA samples from male and female persons with known NL, PM, and FM FMR1 CGG repeats were analyzed. Each FMR1 genotype produced a unique GeneScan electropherogram pattern, thus providing a way to identify the various disease states. The number of CGG repeats in all NL and PM alleles were determined accurately. Analysis by both the new assay and Southern blot of a family segregating with FXS showed complete concordance between both methods. Conclusions: This simplified molecular diagnostic test, based on fluorescent methylation-specific PCR, may be a suitable alternative or complement to Southern blot analysis for the diagnosis of FXS.

scholarly journals New Targeted Treatments for Fragile X Syndrome

2019 ◽  
Vol 15 (4) ◽  
pp. 251-258 ◽  
Author(s):  
Dragana Protic ◽  
Maria J. Salcedo-Arellano ◽  
Jeanne Barbara Dy ◽  
Laura A. Potter ◽  
Randi J. Hagerman
Keyword(s):  
Mental Retardation ◽  
Intellectual Disability ◽  
Fragile X Syndrome ◽  
Behavioral Problems ◽  
Rna Binding ◽  
Fragile X ◽  
Symptomatic Treatment ◽  
Fmr1 Gene ◽  
Fragile X Mental Retardation ◽  
Cgg Repeats

Fragile X Syndrome (FXS) is the most common cause of inherited intellectual disability with prevalence rates estimated to be 1:5,000 in males and 1:8,000 in females. The increase of >200 Cytosine Guanine Guanine (CGG) repeats in the 5’ untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene results in transcriptional silencing on the FMR1 gene with a subsequent reduction or absence of fragile X mental retardation protein (FMRP), an RNA binding protein involved in the maturation and elimination of synapses. In addition to intellectual disability, common features of FXS are behavioral problems, autism, language deficits and atypical physical features. There are still no currently approved curative therapies for FXS, and clinical management continues to focus on symptomatic treatment of comorbid behaviors and psychiatric problems. Here we discuss several treatments that target the neurobiological pathway abnormal in FXS. These medications are clinically available at present and the data suggest that these medications can be helpful for those with FXS.

scholarly journals The fragile X syndrome: 13 years of experience

2011 ◽  
Vol 65 (3-4) ◽  
pp. 67-72
Author(s):  
Zanda Daneberga ◽  
Zita Krūmiņa ◽  
Baiba Lāce ◽  
Daiga Bauze ◽  
Rita Lugovska
Keyword(s):  
Fragile X Syndrome ◽  
Dna Analysis ◽  
Clinical Symptoms ◽  
Cpg Island ◽  
Fragile X ◽  
Psychomotor Development ◽  
Molecular Diagnostic ◽  
Years Of Experience ◽  
Male Population ◽  
Cgg Repeats

The fragile X syndrome: 13 years of experience Fragile X syndrome (FXS; MIM #300624; FRAXA, Xq27.3) is well known and a common cause of X-linked mental retardation. The syndrome is caused by dynamic mutation of FMR1 gene CpG island CGG repeats. Clinically FXS patients demonstrate delayed developmental milestones, particularly speech, attention-deficit/hyperactivity disorder, autistic features, and psychomotor development delay. Dysmorphic face and macroorchidism are important features in the postpubertal age. We present our 13-year experience with FXS patients who were confirmed by molecular diagnostic. Phenotype-genotype evaluation was made for 12 male FXS patients. Genotype-phenotype analysis did not reveal significant correlation between clinical symptoms observed in FXS patients and genotypes obtained from leucocytes DNA analysis. The prevalence of the fragile X syndrome in the Latvian male population was estimated to be 1/6428 (95% CI 5538-7552) or 15.55/100 000 males (95% CI 13.24 - 18.05). The prevalence of the fragile X syndrome among mentally retarded male patients was estimated to be 2.67%. The low number of diagnosed patients with fragile X syndrome demonstrated in our study led to the conclusion that fragile X syndrome is generally clinically unrecognised.

scholarly journals Fragile X Syndrome

2014 ◽  
pp. 190-198 ◽  
Author(s):  
Wilmar Saldarriaga ◽  
Flora Tassone ◽  
Laura Yuriko González-Teshima ◽  
Jose Vicente Forero-Forero ◽  
Sebastián Ayala-Zapata ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Intellectual Disability ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Gene Promoter ◽  
Molecular Techniques ◽  
Pharmaceutical Management ◽  
Developmental Problems ◽  
Fragile X Mental Retardation ◽  
Cgg Repeats

Fragile X Syndrome (FXS) is a genetic disease due to a CGG trinucleotide expansion, named full mutation (greater than 200 CGG repeats), in the fragile X mental retardation 1 gene locus Xq27.3; which leads to an hypermethylated region in the gene promoter therefore silencing it and lowering the expression levels of the fragile X mental retardation 1, a protein involved in synaptic plasticity and maturation. Individuals with FXS present with intellectual disability, autism, hyperactivity, long face, large or prominent ears and macroorchidism at puberty and thereafter. Most of the young children with FXS will present with language delay, sensory hyper arousal and anxiety. Girls are less affected than boys, only 25% have intellectual disability. Given the genomic features of the syndrome, there are patients with a number of triplet repeats between 55 and 200, known as premutation carriers. Most carriers have a normal IQ but some have developmental problems. The diagnosis of FXS has evolved from karyotype with special culture medium, to molecular techniques that are more sensitive and specific including PCR and Southern Blot. During the last decade, the advances in the knowledge of FXS, has led to the development of investigations on pharmaceutical management or targeted treatments for FXS. Minocycline and sertraline have shown efficacy in children.

scholarly journals Fragile X Syndrome in Mentally Retarded Patients from Latvia

2009 ◽  
Vol 63 (1-2) ◽  
pp. 70-72
Author(s):  
Zanda Daneberga ◽  
Zita Krūmiņa ◽  
Baiba Lāce ◽  
Daiga Bauze ◽  
Natālija Proņina ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Fragile X Syndrome ◽  
Detection Rate ◽  
Fragile X ◽  
Mentally Retarded ◽  
Normal Allele ◽  
Cgg Repeat ◽  
Repeat Structure ◽  
Cgg Repeats ◽  
Intermediate Alleles

Fragile X Syndrome in Mentally Retarded Patients from Latvia The aim of this study was to estimate the prevalence of FXS in Latvia and characterise the FMR1 CGG-repeat structure in Latvian patients exhibiting mental retardation. A group of 352 unrelated patients with mental retardation (MR) referred from clinical geneticists was screened by PCR for the normal allele. In a sample of 245 chromosomes the CGG repeat number was determined by Applied Biosystems protocol on ABI Prism 310. Prevalence of 29, 30, and 31 CGG repeats was found for the normal allele. Five affected patients were detected (detection rate 2.56%). AGG interspersion pattern analysis showed stability of transmission to the next generation for 12 intermediate alleles. The found detection rate of FXS in our survey among MR patients was similar to the detection rate reported in literature. Taking into account the number of confirmed FXS cases we suggest that FXS is still clinically unrecognized in paediatrician practice.

scholarly journals An Origin of DNA Replication in the Promoter Region of the Human Fragile X Mental Retardation (FMR1) Gene

2006 ◽  
Vol 27 (2) ◽  
pp. 426-437 ◽  
Author(s):  
Steven J. Gray ◽  
Jeannine Gerhardt ◽  
Walter Doerfler ◽  
Lawrence E. Small ◽  
Ellen Fanning
Keyword(s):  
Mental Retardation ◽  
Dna Replication ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Model Systems ◽  
Fmr1 Gene ◽  
Fragile X Mental Retardation ◽  
Cgg Repeats ◽  
Origin Of Dna Replication ◽  
Transformed Cell Lines

ABSTRACT Fragile X syndrome, the most common form of inherited mental retardation in males, arises when the normally stable 5 to 50 CGG repeats in the 5′ untranslated region of the fragile X mental retardation protein 1 (FMR1) gene expand to over 200, leading to DNA methylation and silencing of the FMR1 promoter. Although the events that trigger local CGG expansion remain unknown, the stability of trinucleotide repeat tracts is affected by their position relative to an origin of DNA replication in model systems. Origins of DNA replication in the FMR1 locus have not yet been described. Here, we report an origin of replication adjacent to the FMR1 promoter and CGG repeats that was identified by scanning a 35-kb region. Prereplication proteins Orc3p and Mcm4p bind to chromatin in the FMR1 initiation region in vivo. The position of the FMR1 origin relative to the CGG repeats is consistent with a role in repeat maintenance. The FMR1 origin is active in transformed cell lines, fibroblasts from healthy individuals, fibroblasts from patients with fragile X syndrome, and fetal cells as early as 8 weeks old. The potential role of the FMR1 origin in CGG tract instability is discussed.

scholarly journals Fragile X syndrome in Calcutta, India

2001 ◽  
Vol 38 (3) ◽  
pp. 264-271 ◽  
Author(s):  
Sharmila Saha ◽  
Parimal Karmakar ◽  
Chandrahas Chatterjee ◽  
Dalia Banerjee ◽  
Shyamal Das ◽  
...  
Keyword(s):  
Mental Retardation ◽  
Fragile X Syndrome ◽  
Clinical Features ◽  
Untranslated Region ◽  
Fragile X ◽  
Eastern Region ◽  
Ethnic Variation ◽  
Cgg Repeat ◽  
Repeat Size ◽  
Cgg Repeats

Fragile-X-linked mental retardation usually results from amplification of the CGG repeat in the 5' untranslated region of the FMR1 gene. To assess the extent of variation of the CGG repeat in the population from the eastern region of India we studied 98 mentally retarded individuals living in and around Calcutta and identified 21 distinct alleles ranging in size from 8 to 44 CGG repeats. A repeat size of 28 was the most frequent; this value is different from the most frequent repeat size found in other studies, indicating a racial or ethnic variation. Patients with the clinical features of the syndrome have been found to carry expanded CGG repeats. Thus, it can be inferred that the expansion of CGG repeats may be a frequent cause of the syndrome in our population.

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