The full mutation in the FMR–1 gene of male fragile X patients is absent in their sperm

Reyniers, Edwin; Vits, Lieve; Boulle, Kristel De; Roy, Bernadette Van; Velzen, Désiré van; Graaff, Esther de; Verkerk, Annemieke J.M.H.; Jorens, Hugo Z.J.; Darby, John; Oostra, Ben A.

doi:10.1038/ng0693-143

Cited by 238 publications

(135 citation statements)

References 42 publications

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“…21,22 Furthermore, although males with full mutations have full mutation alleles in their somatic cells, only premutation size alleles are present in sperm. 23 This is in stark contrast to full mutation expansions that occur, with increasing likelihood in female transmissions as allele size increases.…”

Section: Discussionmentioning

confidence: 91%

Fragile X full mutation expansions are inhibited by one or more AGG interruptions in premutation carriers

Nolin

Glicksman

Ersalesi

et al. 2015

Genetics in Medicine

122

131

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AGGs. Two contractions in maternal transmission were accompanied by loss of AGGs, suggesting a mechanism for generating alleles that lack AGG interruptions. Maternal age was examined as a factor in full mutation expansions using prenatal samples to minimize ascertainment bias, and a possible effect was observed though it was not statistically significant (P = 0.06). Conclusion:These results strengthen the association of AGG repeats with CGG repeat stability and provide more accurate risk estimates of full mutation expansions for women with 45-90 repeat alleles.

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Section: Discussionmentioning

confidence: 91%

Fragile X full mutation expansions are inhibited by one or more AGG interruptions in premutation carriers

Nolin

Glicksman

Ersalesi

et al. 2015

Genetics in Medicine

122

131

View full text Add to dashboard Cite

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“…In the fragile X syndrome, expansion of the trinucleotide repeat in the FMR1 gene from the premutation to the full mutation occurs exclusively when the mutation is inherited from the female (15). However, since the full mutation is absent from sperm of fragile X males, these expansions may be mitotic, occurring in the somatic cells of the affected offspring (16). Expansion of trinucleotide repeats in other disorders is also influenced by the sex of origin.…”

Section: Discussionmentioning

confidence: 99%

Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells

et al. 1994

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The factor VIII gene, which Is defective In hemophilia A, Is located In the last megabase of the long arm of the X chromosome. Inversions due to intrachromosomal homologous recombination between mispaired copies of gene A located within intron 22 of the gene and about 500 kb telomerlc to it account for nearly half of all cases of severe hemophilia A. We hypothesized that pairing of Xq with its homolog inhibits the Inversion process, and that, therefore, the event originates predominantly in male germ cells. In all 20 informative cases In which the inversion originated in a maternal grandparent, DNA polymorphism analysis determined that it occurred in the male germline. In addition, all but one of 50 mothers of sporadic cases due to an inversion were carriers. Thus, these data support the hypothesis and Indicate that factor VIII gene inversions leading to severe hemophilia A occur almost exclusively In male germ cells.

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“…In 1993, Reyniers et al (33) showed the presence of a premutation and not a full mutation in sperm of patients with a full mutation in their blood cells. From this they postulated two hypotheses on the possible timing of the CGG repeat amplification.…”

Section: Discussionmentioning

confidence: 99%

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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The full mutation in the FMR–1 gene of male fragile X patients is absent in their sperm

Cited by 238 publications

References 42 publications

Fragile X full mutation expansions are inhibited by one or more AGG interruptions in premutation carriers

Fragile X full mutation expansions are inhibited by one or more AGG interruptions in premutation carriers

Factor VIII gene inversions causing severe hemophilia A originate almost exclusively in male germ cells

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

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