Autosomal suppressor gene for fragile‐X: An hypothesis

Publisher Website
Google Scholar
Abstract
We suggest the existence of an autosomal suppressor gene, S, which is fairly common in the general population and acts to inhibit expression of the fra(X) gene, F. The suppression is effective in males who are hemizygous for F only if they are homozygous for S, while it is effective in females who are heterozygous for F if they are at least heterozygous for S. Thus, the fra(X) phenotype is not expressed in genotypes F-SS, FfSS, FfSs, while it is expressed in genotypes F-Ss, F-ss, Ffss. With a frequency of SS in the general population of approximately 20%, this hypothesis can explain the observed penetrance of about 80% in F- males and about 30% in Ff females. It can also explain the very low frequency of fra(X) expression in Ff females who are daughters or mothers of non-penetrant F- males, and a lower penetrance in siblings of non-penetrant F- males than in grandsons of these males. The model is in good quantitative agreement with other unique characteristics of fra(X) inheritance.