The identification of a third fragile site, FRAXF, in Xq27 — q28 distal to both FRAXA and FRAXE

Hirst, Mark C.; Barnicoat, Angela; Flynn, Geraldine; Wang, Q.; Daker, M. G.; Buckle, Veronica J.; Davies, Kay E.; Bobrow, Martin

doi:10.1093/hmg/2.2.197

Cited by 56 publications

(20 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 Since then it was reported only in a small number of additional cases. 3 In contrary to the other two more proximal Xq27.3-q28 folate sensitive fragile sites, FRAXA and FRAXE, FRAXF was considered benign.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A novel gene, FAM11A, associated with the FRAXF CpG island is transcriptionally silent in FRAXF full mutation

et al. 2002

View full text Add to dashboard Cite

The cytogenetic expression of the FRAXF fragile site is due to an expanded, hypermethylated and unstable CGG repeat in Xq28. Normal individuals have 6 -38 triplet repeats while individuals expressing the fragile site have expansions of greater than 300 triplets. Through analysis of the region adjacent to the fragile site, we have identified a *2.6 kb cDNA originating from the FRAXF fragile site associated CpG island, and containing the unstable FRAXF CGG repeat in its 5' UTR region. This gene, FAM11A, comprises at least seven exons, shows alternative splicing, and extends over 35 kb of genomic DNA distal to the FRAXF fragile site. Analysis of the FAM11A cDNA sequence has identified a 1050 bp open reading frame encoding a 350 amino acid protein. We have also identified FAM11B a highly conserved (88% at the protein level) transcribed chromosome 2 retropseudogene. We show that the novel FRAXF fragile site associated gene FAM11A is transcriptionally silenced in a normal individual with a cytogenetically and molecularly detectable FRAXF CGG full mutation (fragile site). Finally, we were able to reactivate FAM11A transcription by treatment of a FRAXF lymphoblastoid cell line with the demethylating agent 5-azadeoxycytidine, thus demonstrating the critical role of FRAXF methylation in FAM11A silencing.

show abstract

Section: Discussionmentioning

confidence: 99%

“…It was originally identified in 1993 in a family with developmental delay. 1 Since then, it has been seen in only a small number of additional families tested cytogenetically because of MR or developmental delay. 1 -4 In addition to FRAXF there are two other folate sensitive fragile sites in Xq27-28, FRAXA and FRAXE.…”

Section: Introductionmentioning

confidence: 99%

A novel gene, FAM11A, associated with the FRAXF CpG island is transcriptionally silent in FRAXF full mutation

et al. 2002

View full text Add to dashboard Cite

show abstract

“…The high frequency of fragile X positive cytogenetic results in Taiwan [Li et al, 1988] and in central (7.6%) and northeast (5.0%) mainland China (Table I) may have resulted from the difficulty of distinguishing the FRAXA fragile site from two other fragile sites, the FRAXE and FRAXF Hirst et al, 1993]. Both FRAXE and FRAXF are located in a similar region at Xq27.3-8.…”

Section: Discussionmentioning

confidence: 99%

Frequency of the fragile X syndrome in Chinese mentally retarded populations is similar to that in Caucasians

Zhong

et al. 1999

Am. J. Med. Genet.

View full text Add to dashboard Cite

Fragile X syndrome is recognized as the most common inherited cause of mental retardation in western countries. The prevalence of the fragile X syndrome in Asian populations is uncertain. We report a multi-institutional collaborative study of molecular screening for the fragile X syndrome from 1,127 Chinese mentally retarded (MR) individuals. We found that 2.8% of the Chinese MR population screened by DNA analysis had the fragile X full mutation. Our screening indicated that the fragile X syndrome prevalence was very close to that of Caucasian subjects. In addition, we found that 62.5% of fragile X chromosomes had a single haplotype for DXS548-FRAXAC1 (21-18 repeats) which was present in only 9.7% of controls. This unique distribution of microsatellite markers flanking the FMR1 CGG repeats suggests that the fragile X syndrome in Chinese populations, as in the Caucasian, may also be derived from founder chromosomes.

show abstract

“…85,88 Three other fragile sites are caused by repeat expansions. FRAXF (a CCG repeat), 89 FRA16A (a CCG repeat), 90 and FRA16B (an A-T rich repeat 33 nucleotides in length) 91 are not associated with a phenotype. FRA11B, resulting from a CGG expansion in the untranslated region of the protooncogene CBL2, is associated with in deletion of the distal portion of chromosome 11q.…”

Section: The Expansion Mutation Diseasesmentioning

confidence: 99%

Trinucleotide Repeat Expansion and Neuropsychiatric Disease

Margolis¹,

McInnis²,

Rosenblatt³

et al. 1999

Arch Gen Psychiatry

View full text Add to dashboard Cite

Trinucleotide, or triplet, repeats consist of 3 nucleotides consecutively repeated (e.g., CCG CCG CCG CCG CCG) within a region of DNA, a not uncommon motif in the genome of humans and other species. In 1991, a new type of genetic mutation was discovered, known as a dynamic or expansion mutation, in which the number of triplets in a repeat increases and the length becomes unstable. During the past decade, nearly 20 diseases-including Huntington disease, 2 forms of the fragile X syndrome, and myotonic dystrophy-caused by trinucleotide repeat expansions have been identified. The unstable nature of the expanded repeat leads to remarkable patterns of inheritance in these diseases, distinctly at odds with traditional notions of mendelian genetics. We review the clinical and genetic features of these disorders, with a particular emphasis on their psychiatric manifestations. We also critically examine the hypothesis that expansion mutations may have an etiologic role in psychiatric diseases such as bipolar disorder, schizophrenia, and autism.

show abstract

The identification of a third fragile site, FRAXF, in Xq27 — q28 distal to both FRAXA and FRAXE

Cited by 56 publications

References 0 publications

A novel gene, FAM11A, associated with the FRAXF CpG island is transcriptionally silent in FRAXF full mutation

A novel gene, FAM11A, associated with the FRAXF CpG island is transcriptionally silent in FRAXF full mutation

Frequency of the fragile X syndrome in Chinese mentally retarded populations is similar to that in Caucasians

Trinucleotide Repeat Expansion and Neuropsychiatric Disease

Contact Info

Product

Resources

About