The molecular basis of the folate-sensitive fragile site FRA11A at 11q13
K Debacker1, B Winnepenninckx, C Longman
1Department of Medical Genetics, University of Antwerp, Belgium.
Abstract:
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.
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