Parental origin of the Fra(X) gene is a major determinant of the cytogenetic expression and the CGG repeat length in female carriers

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Abstract
The fragile X [fra(X)] syndrome is the most frequent form of inherited mental retardation, and co‐segregates with a fragile site at Xq27.3 as well as with insertion of a variable number of trinucleotide repeats in the 5′‐end of the FMR‐1 gene. As the fra(X) gene is transmitted by females as well as males, we have investigated whether the parental origin of the fra(X) gene has an effect upon the cytogenetic expression and CGG repeat length. An increased fragment length of 0.2 ‐ 0.6 kb appeared to be associated with a very low expression or even complete absence of the fragile site as well as with a normal phenotype, and was seen mostly in cases of paternal inheritance. However, in most female carriers with the maternally inherited fra(X) gene we found dispersed fragments ranging from 1.4 ‐ 6.5 kb or even complete absence of a hybridization signal. Within the group of female carriers with the maternally inherited fra(X) gene we found a statistically significant correlation between the level of the cytogenetic expression and the PstI restriction fragment length encompassing the CGG repeat. These data can be taken as indirect evidence that CGG repeat length and cytogenetic expression are causally related.