The molecular basis of the folate-sensitive fragile site FRA11A at 11q13.
We report on the molecular basis of the rare, folate-sensitive fragile site FRA11A in chromosome band 11q13 in a family with cytogenetic expression. Five individuals express the fragile site and one was mentally retarded. Expansion of a polymorphic CGG-repeat located at the 5' end of the C11orf80 gene causes FRA11A. The CGG-repeat elongation coincides with hypermethylation of the adjacent CpG island and subsequent transcriptional silencing of the C11orf80 gene. This gene has no homology with known genes. A relationship between cytogenetic expression of the fragile site and the mental handicap seems unlikely, as FRA11A was found in a mentally retarded patient as well as in phenotypically normal carriers from the same family. However, incomplete penetrance cannot be entirely excluded.
Debacker
K
K
Department of Medical Genetics, University of Antwerp, Belgium.
Winnepenninckx
B
B
Longman
C
C
Colgan
J
J
Tolmie
J
J
Murray
R
R
van Luijk
R
R
Scheers
S
S
Fitzpatrick
D
D
Kooy
F
F
D043283:Chromosome Fragile Sites / Q000187:drug effects* / Q000235:genetics*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D019295:Computational Biology; D005260:Female; D005492:Folic Acid / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D010375:Pedigree; D010641:Phenotype
D005492:Folic Acid