Mental impairment in Martin-Bell syndrome is probably determined by interaction of several genes: simple explanation of phenotypic differences between unaffected and affected males with the same X chromosome

Summary

A family with Martin-Bell syndrome (MBS) is described with transmission of this X-linked trait by a normal male who manifested the fragile site at Xq27. This family shows features apparently typical for all families with a normal male transmitter. The daughters of this male are mentally normal and their fragile site is difficult or impossible to detect but detection of the heterozygous genotype is much easier among the granddaughters. This can be explained by a model assuming that mental deficiency in patients with MBS is determined by several genes, i.e. the X-linked MBS-gene as “major gene” undergoing X-inactivation and interacting with at least one modifying gene. The model assuming one autosomal modifier segregating independently from the MBS-gene is tested using the results of segregation analysis performed by Sherman et al. (1984, 1985). No significant differences have been found between the predictions of this model and the findings of the segregation analysis. Nearly all of the segregation data are exactly predicted by the model. Possible differences are discussed either to be due to biased data or to require slight modification of the model to get a better fit of the data. The apparent phenotypic differences between a normal carrier grand-father and his affected grandsons as well as between his daughters and his heterozygous granddaughters are also simply explained on the basis of this model. Several modifier loci may exist each of them related to one of the various phenotypic effects of the X-linked major gene (MBS-gene) leading typic effects of the X-linked major gene (MBS-gene) leading to a syndrome that does not include any obligate feature.