Fragile X syndrome and the (CGG)n mutation

Two families with discordant MZ twins

Helena Kruyer, Montserrat Milà, Guillermo Glover, Pablo Carbonell, Francisca Ballesta, Xavier P. Estivill

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

The fragile X phenotype has been found, in the majority of cases, to be due to the expansion of a CGG repeat in the 5′ UTR region of the FMR-1 gene, accompanied by methylation of the adjacent CpG island and inactivation of the FMR-1 gene. Although several important aspects of the genetics of fragile X have been resolved, it remains to be elucidated at which stage in development the transition from the premutation to the full mutation occurs. We present two families in which discordance between two sets of MZ twins illustrates two important genetic points. In one family, two affected MZ brothers differed in the number of CGC repeats, demonstrating in vivo mitotic instability of this CGG repeat and suggesting that the transition to the full mutation occurred postzygotically. In the second family, two MZ sisters had the same number of repeats, but only one was mentally retarded. When the methylation status of the FMR-1 CpG island was studied, we found that the majority of normal chromosomes had been inactivated in the affected twin, thus leading to the expression of the fragile X phenotype.

Original languageEnglish
Pages (from-to)437-442
Number of pages6
JournalAmerican Journal of Human Genetics
Volume54
Issue number3
Publication statusPublished - 1994
Externally publishedYes

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Fragile X Syndrome
CpG Islands
Methylation
Mutation
Siblings
Phenotype
5' Untranslated Regions
Mentally Disabled Persons
Genes
Chromosomes

ASJC Scopus subject areas

  • Genetics

Cite this

Kruyer, H., Milà, M., Glover, G., Carbonell, P., Ballesta, F., & Estivill, X. P. (1994). Fragile X syndrome and the (CGG)n mutation: Two families with discordant MZ twins. American Journal of Human Genetics, 54(3), 437-442.

Fragile X syndrome and the (CGG)n mutation : Two families with discordant MZ twins. / Kruyer, Helena; Milà, Montserrat; Glover, Guillermo; Carbonell, Pablo; Ballesta, Francisca; Estivill, Xavier P.

In: American Journal of Human Genetics, Vol. 54, No. 3, 1994, p. 437-442.

Research output: Contribution to journalArticle

Kruyer, H, Milà, M, Glover, G, Carbonell, P, Ballesta, F & Estivill, XP 1994, 'Fragile X syndrome and the (CGG)n mutation: Two families with discordant MZ twins', American Journal of Human Genetics, vol. 54, no. 3, pp. 437-442.
Kruyer, Helena ; Milà, Montserrat ; Glover, Guillermo ; Carbonell, Pablo ; Ballesta, Francisca ; Estivill, Xavier P. / Fragile X syndrome and the (CGG)n mutation : Two families with discordant MZ twins. In: American Journal of Human Genetics. 1994 ; Vol. 54, No. 3. pp. 437-442.
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