Possible Erasure of the Imprint on a Fragile X Chromosome When Transmitted by a Male

Abstract

Although most males with the fragile‐X [fra(X)] syndrome do not reproduce, there are 2 published pedigrees that include affected males who have daughters and who thus appear to have transmitted the fragile‐X chromosome to their progeny. In addition, one published fra(X) pedigree includes an apparently normal male who expresses cytogenetically the fra(X) site at high frequency and who has 3 daughters. In the 6 daughters of these 3 males, there is little or no cytogenetic expression of the fra(X). I interpret these pedigrees within the context of my X‐inactivation imprinting model of the fra(X) syndrome (Genetics 117:587–599): the cytogenetic manifestation of the imprinted state of the mutant fra(X) chromosome [high percentage of cytogenetic expression] is no longer present in daughters of imprinted males. I propose that the imprinted state is erased when an imprinted fragile‐X chromosome is passed through a male. Such erasure in the gender opposite to the gender that established the imprint is in accord with other examples of chromosome imprinting in mammals. Additional data from unpublished fra(X) pedigrees are requested.