To the Editor.—
In the April 1990 issue of the Archives,1 Berrettini et al analyzed nine bipolar pedigrees for linkage to three DNA loci in the Xq28 region and excluded a gene for bipolar illness from 30 centimorgans of that region. One explanation of nonreplication of X-chromosome linkage findings is genetic heterogeneity, as noted by Berrettini et al. Therefore, it is important to exclude pedigrees exhibiting father-son transmission, since they are inconsistent with X linkage. Pedigree 0048 in the study by Berrettini et al included two affected sons, one with bipolar illness and the other with cyclothymic personality disorder, connected to the pedigree by an unaffected father. The pedigree was included on the grounds that the illness in the sons could have come from their mother. However, no mention was made of affective disorder in the mother or her family. Therefore, while the authors' statement that nowhere in