Premutation for the Martin-Bell syndrome analyzed in a large Sardinian family: III. Molecular analysis with the...

This report complements a series of clinical, cytogenetical, and psychological studies previously reported on a large Sardinian pedigree segregating for premutations and full mutations associated with the Martin-Bell syndrome (MBS). Using the StB12.3 probe, we report now the molecular classification of all of the critical members of the pedigree. These molecular findings are evaluated against the variable phenotypic manifestations of the disease in the course of a six-generation segregation of an MBS premutation allegedly present in a common female progenitor of 14 MBS male patients and 9 female MBS heterozygotes seen in the last two generations. The nature and stepwise progression of MBS-premutations toward the fully manifested Martin-Bell syndrome and the possibility of reverse mutational events toward the normal allele are discussed with respect to the application of the presently available diagnostic tools in genetic counselling.