Mental Status and Fragile X Expression in Relation to FMR-1 Gene Mutation

Bb, de Vries; Wiegers, AM; E, de Graaff; Verkerk, Annemieke J.M.H.; Jo, van Hemel; Dj, Halley; Jp, Fryns; Lm, Curfs; Mf, Niermeijer; Ba, Oostra

doi:10.1159/000472389

Cited by 65 publications

(38 citation statements)

References 25 publications

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“…Rearrangements associated with triplet repeats have been noted previously for E. coli (24,25,57) and in patients with fragile X syndrome (13,15,45,47,69). The characterized fragile X rearrangements include deletions that encompass the CGG repeat (13,69) and deletions that have one end within the repeat (45,47), which are similar to the types of rearrangements that we have identified for CTG repeats.…”

Section: Discussionsupporting

confidence: 80%

Long CTG Tracts from the Myotonic Dystrophy Gene Induce Deletions and Rearrangements during Recombination at the APRT Locus in CHO Cells

Meservy¹,

Sargent²,

Iyer

et al. 2003

Molecular and Cellular Biology

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Expansion of CTG triplet repeats in the 3 untranslated region of the DMPK gene causes the autosomal dominant disorder myotonic dystrophy. Instability of CTG repeats is thought to arise from their capacity to form hairpin DNA structures. How these structures interact with various aspects of DNA metabolism has been studied intensely for Escherichia coli and Saccharomyces cerevisiae but is relatively uncharacterized in mammalian cells. To examine the stability of (CTG) 17 , (CTG) 98 , and (CTG) 183 repeats during homologous recombination, we placed them in the second intron of one copy of a tandemly duplicated pair of APRT genes. Cells selected for homologous recombination between the two copies of the APRT gene displayed distinctive patterns of change. Among recombinants from cells with (CTG) 98 and (CTG) 183 , 5% had lost large numbers of repeats and 10% had suffered rearrangements, a frequency more than 50-fold above normal levels. Analysis of individual rearrangements confirmed the involvement of the CTG repeats. Similar changes were not observed in proliferating (CTG) 98 and (CTG) 183 cells that were not recombinant at APRT. Instead, they displayed high frequencies of small changes in repeat number. The (CTG) 17 repeats were stable in all assays. These studies indicate that homologous recombination strongly destabilizes long tracts of CTG repeats.

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Section: Discussionsupporting

confidence: 80%

Long CTG Tracts from the Myotonic Dystrophy Gene Induce Deletions and Rearrangements during Recombination at the APRT Locus in CHO Cells

Meservy¹,

Sargent²,

Iyer

et al. 2003

Molecular and Cellular Biology

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“…Patient 1 has a Prader-Willi like phenotype and was previously described by de Vries et ai (46). The three other patients have the classical M artin-B ell phenotype.…”

Section: Patientsmentioning

confidence: 69%

Hotspot for deletions in the CGG repeat region of FMR1 in fragile X patients

Graaff¹,

Rouillard

Willems

et al. 1995

Human Molecular Genetics

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The fragile X syndrome is the most frequent cause of inherited mental retardation. The molecular mechanism of the disorder is based on the expansion of a CGG repeat in the 5' UTR of the FMR1 gene in the majority of fragile X patients. The instability of this CGG repeat containing region is not restricted to the CGG repeat itself but expands to the flanking region as well. We describe four unrelated fragile X patients that are mosaic for both a full mutation and a small deletion in the CGG repeat containing region. Sequence analysis of the regions surrounding the deletions showed that both the (CGG)n repeat and some flanking sequences were missing in all four patients. The 5' breakpoints of the deletions were found to be located between 75-53 bp proximal to the CGG repeat. This suggests the presence of a hot spot region for deletions in the CGG repeat region of the FMR1 gene and emphasizes the instability of this region in the presence of an expanded CGG repeat.

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“…This is consistent with the recent report in which it was found that the degree of mental retardation in most prepubertal fragile X males is moderate, and in adults it is moderate to severe. [32][33] A correlation between macro-orchidism and fragile X syndrome has also been reported, however, macroorchidism is generally difficult to identify early in life and is frequently absent in younger patients. [1][2] However, different frequencies of fragile X-positive cases were reported among patients with macro-orchidism as one of the clinical features; this figure ranges from 11% to 80%.…”

Section: Discussionmentioning

confidence: 99%