© 1992 Oxford University Press
RESEARCH-ARTICLE |
Segregation of the fragile X mutation from an affected male to his normal daughter
Department of Medical Genetics, University of Antwerp—UIA 2610 Antwerp, Belgium 1Departments of Clinical Genetics, Erasmus University Rotterdam The Netherlands 2Departments of Cell Biology, Erasmus University Rotterdam The Netherlands
*To whom correspondence should be addressed
Received June 19, 1992; Revised August 14, 1992; Accepted August 14, 1992
We report here a family in which the fragile X mutation segregates from an affected grandfather through his normal daughter to an affected grandson. The grandson shows clinical and cytogenetic expression of fragile X syndrome due to a full mutation (large methylated insertion) in the fragile X gene (FMR-1). The mother shows a premutation (small unmethylated insertion) in her FMR-1 gene as the sole manifestation of the fragile X syndrome. The grandfather expresses the fragile X syndrome at the clinical and cytogenetic level, whereas he is mosaic for a methylated full mutation and an unmethylated premutation. The absence of expression of the fragile X mutation when transmitted through an expressing male might present further evidence for genomic imprinting of the FMR-1 gene. Alternatively, it is possible that the grandfather transmitted his premutation to his daughter due to germline mosaicism with both the premutation and the full mutation present in his sperm.