The molecular genetics of the human I locus and molecular background explain the partial association of the adult i phenotype with congenital cataracts.

The human i and I antigens are characterized as linear and branched repeats of N-acetyllactosamine, respectively. Conversion of the i to the I structure requires I-branching beta-1,6-N-acetylglucosaminyltransferase activity. It has been noted that the null phenotype of I, the adult i phenotype, is associated with congenital cataracts in Asians. Previously, the identification of molecular changes in the IGnT gene, associated with the adult i phenotype, has been reported. In the present study, we demonstrate that the human I locus expresses 3 IGnT forms, designated IGnTA, IGnTB, and IGnTC, which have different exon 1, but identical exons 2 and 3, coding regions. The molecular genetics proposed for the I locus offer a new perspective on the formation and expression of the I antigen in different cells and provide insight into the questions derived from investigation of the adult i phenotype. Molecular genetic analyses of the I loci of the 2 adult i groups, with and without congenital cataracts, were performed, and enzyme function assays and expression patterns for the 3 IGnT transcripts in reticulocytes and lens-epithelium cells were analyzed. The results suggest a molecular genetic mechanism that may explain the partial association of the adult i phenotype with congenital cataracts and indicate that a defect in the I locus may lead directly to the development of congenital cataracts. The results also suggest that the human blood group I gene should be reassigned to the IGnTC form, not the IGnTB form, as described previously.