Prenatal Diagnosis of Fragile X Syndrome by Direct Detection of the Unstable DNA Sequence

Sutherland, Grant R.; Gedeon, Agi; Kornman, Louise; Donnelly, Andrew J.; Byard, Roger W.; Mulley, John C.; Kremer, Eric J.; Lynch, Michael; Pritchard, Melanie April; Yu, Shaohua; Richards, Robert I.

doi:10.1056/nejm199112123252407

Cited by 84 publications

(34 citation statements)

References 8 publications

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“…In the same manner, not detecting the full mutation's smear in a 'mosaic' (male or female) would lead to the false conclusion that they carry only a premutation and are not at risk of mental retardation. The Sac11 enzyme to identify DNA methylation has proved to be too insensitive [55], probably because the two Sac11 restriction sites are further away from the mutation than the EagI or BssHII sites [20]. Southern blot methods allow estimation of the approximate size of the fragile X expansion and the results are generally reported as the size difference A (in base pairs) between the mutation and the most frequent normal allele.…”

Section: Dna Testingmentioning

confidence: 99%

“…Genotypic analysis can be carried out on chorionic villi (30 mg is necessary for Southern blot analysis) and will readily identify any fragile X mutation as well as sex determination [29,55]. However, the methylation status is usually not completely established in chorionic villi and can complicate differentiation of premutations from full mutations for As between 400bp and 700bp [29].…”

Section: Prenatal Diagnosismentioning

confidence: 99%

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The fragile X syndrome: implications of molecular genetics for the clinical syndrome

Rousseau

1994

Eur J Clin Investigation

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Abstract. The fragile X syndrome of mental retardation is one of the most common genetic diseases. Characterization of the mutations involved has greatly improved our knowledge of the transmission of fragile X syndrome and new DNA-based diagnostics tools significantly outperform cytogenetic testing both for establishing the diagnosis and for determining carrier status. Fragile X mutations consist of an expansion of a CGG trinucleotide repeat localized in a gene (FMR-1) that is abnormally methylated in all affected individuals. They are classified as premutations (asymptomatic) and full mutations (associated with the disease). Several different DNA analysis protocols are used for fragile X genotyping but only a few have been tested on large samples of individuals. There are several clinical indications for direct DNA genotyping for fragile X including mental retardation, learning disability or hyperactivity in children with or without a family history of mental retardation, the establishment of carrier diagnosis in fragile X families and prenatal screening of children from carrier women.

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Section: Dna Testingmentioning

confidence: 99%

Section: Prenatal Diagnosismentioning

confidence: 99%

The fragile X syndrome: implications of molecular genetics for the clinical syndrome

Rousseau

1994

Eur J Clin Investigation

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“…The cloning of the fragile X mental retardation gene [5][6][7] has given rise to new prospects for identifying fragile X patients with direct diagnosis by using PCR analysis and DNA probe in Southern blotting [14,15]. The DNAbased method is the most reliable method for the detection of full mutation, but it generally takes more than 1 week and needs an established laboratory in molecular biology.…”

Section: Discussionmentioning

confidence: 99%

Cytogenetic and Immunohistochemical Characterization of Fragile X Syndrome in a Kuwaiti Family: Rapid Antibody Test for the Diagnosis of Mental Retardation Patients

Alkhalaf

Verghese

Mushtaq³

2001

Med Princ Pract

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Objectives: To study a Kuwaiti family with fragile X mental retardation syndrome and present a rapid, noninvasive antibody test to be used for fragile X syndrome diagnosis on all mentally retarded patients in Kuwait. Methods: For cytogenetic analysis, the fragile site was induced by culturing blood lymphocytes in a medium containing a low concentration of folate (M199) or by adding 0.1 µM of fluorodeoxyuridine to the culture media. For the immunohistochemical test on blood smears, monoclonal antibodies against fragile X mental retardation (FMR1) gene product were used. The test is based on the presence of the protein in lymphocytes from normal individuals and its absence in lymphocytes from fragile X patients. Results: A Kuwaiti family with fragile X syndrome in 4 affected males is described. The immunohistochemical study with the monoclonal antibodies against FMR protein gave conclusive results on the same day for the affected males. Conclusion: To our knowledge, this is the first report describing a large Kuwaiti family with the fragile X syndrome. These data suggest that the immunohistochemical test used is an ideal method for the diagnosis of fragile X syndrome in mentally retarded patients in Kuwait.

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“…Prenatal DNA analysis can be routinely carried out using a chorionic villus sample, as well as after amniocentesis (38,97,104,105). The obvious advantage of chorion villi is the early stage of pregnancy.…”

Section: Mechanism and Timing Of Repeat Amplificationmentioning

confidence: 99%

“…The obvious advantage of chorion villi is the early stage of pregnancy. On the other hand methylation tests can be reliably performed on DNA from amniotic fluid cells, which is not possible on chorion villi DNA (97). The accuracy of the first trimester DNA assay has been shown to be greater than the formerly applied cytogenetic method (97).…”

Section: Mechanism and Timing Of Repeat Amplificationmentioning

confidence: 99%

Complex Behavior of Simple Repeats: The Fragile X Syndrome

Oostra

Halley

1995

Pediatr Res

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Prenatal Diagnosis of Fragile X Syndrome by Direct Detection of the Unstable DNA Sequence

Cited by 84 publications

References 8 publications

The fragile X syndrome: implications of molecular genetics for the clinical syndrome

The fragile X syndrome: implications of molecular genetics for the clinical syndrome

Cytogenetic and Immunohistochemical Characterization of Fragile X Syndrome in a Kuwaiti Family: Rapid Antibody Test for the Diagnosis of Mental Retardation Patients

Complex Behavior of Simple Repeats: The Fragile X Syndrome

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