I BLOOD GROUP SYSTEM
CTRCT13, INCLUDED
I-NULL PHENOTYPE, INCLUDED
CATARACT 13 WITH ADULT i PHENOTYPE, INCLUDED
Ii
Ii BLOOD GROUP SYSTEM ADULT i PHENOTYPE, INCLUDED
The i and I antigens of the I blood group system are carbohydrate structures carried on glycolipids and glycoproteins and are characterized as straight or branched glycochains composed of repeating N-acetyllactosamine (LacNAc) units, respectively. Conversion of i antigen ... The i and I antigens of the I blood group system are carbohydrate structures carried on glycolipids and glycoproteins and are characterized as straight or branched glycochains composed of repeating N-acetyllactosamine (LacNAc) units, respectively. Conversion of i antigen into an I-active structure requires the activity of the I-branching enzyme, beta-1,6-N-acetylglucosaminyltransferase (GCNT2; 600429), which adds the decisive GlcNAc-beta-1-6 branch onto the straight poly-LacNAc chains. Expression of the i and I antigens on red blood cells (RBCs) is reciprocal and developmentally regulated. Adult human RBCs predominantly express I antigen, whereas fetal and neonatal RBCs predominantly express i antigen. After birth, I antigen levels increase gradually as i antigen levels fall, with the normal Ii status of adult RBCs reached after about 13 to 20 months. Mutations that specifically affect 1 of the 3 variants produced by the GCNT2 gene cause the rare adult i phenotype, in which adult RBCs are rich in i antigen and contain low levels of I antigen. Mutations that eliminate all 3 GCNT2 variants cause the adult i phenotype with congenital cataract (see MOLECULAR GENETICS) (review by Yu and Lin, 2011).
Tippett et al. (1960) described a Baltimore black family in which red cells were apparently of i phenotype and their serum contained anti-I. This was the first direct evidence that the I antigen is under genetic control. Anti-I ... Tippett et al. (1960) described a Baltimore black family in which red cells were apparently of i phenotype and their serum contained anti-I. This was the first direct evidence that the I antigen is under genetic control. Anti-I was first identified by Wiener et al. (1956). Yamaguchi et al. (1972) presented evidence suggesting linkage of the Ii blood group locus and a recessive form of congenital cataract. In each of 4 Japanese families, 2 sibs were both homozygous for 'little eye' (no pun intended), and affected with a recessive form of cataract. Ogata et al. (1979) found congenital cataract in 17 of 18 Japanese of the i phenotype. Macdonald et al. (1983) reported a Caucasian family in Australia in which a sister and brother (whose parents were half first cousins, i.e., the offspring of half sisters) had cataracts and the phenotype I-negative, i-positive. Page et al. (1987) observed a 19-year-old woman of Irish descent whose red blood typed as I-negative and i-positive. The patient had bilateral cataracts recognized at birth; there had been no maternal history of German measles or other problems during pregnancy. Page et al. (1987) also studied the blood of 31 Caucasian patients with congenital cataracts and found none with the i phenotype. The pattern of inheritance of cataracts in the 31 patients was either autosomal dominant or apparently sporadic, with no clear instance of autosomal recessive inheritance.
Yu and Lin (2011) reviewed the molecular genetics of the I blood group system and regulation of I antigen expression.
Yu et al. (2001) determined the molecular basis of the adult i phenotype that had been ... Yu and Lin (2011) reviewed the molecular genetics of the I blood group system and regulation of I antigen expression. Yu et al. (2001) determined the molecular basis of the adult i phenotype that had been found to be associated with congenital cataract in 3 Taiwanese 'adult i pedigrees' by Lin-Chu et al. (1991). In 2 of the families, the affected individuals were compound heterozygotes for the same 2 mutations of the GCNT2 gene (600429.0001); in the third family, with first-cousin parents, the affected individuals were homozygous for deletion of the GCNT2 gene (600429.0003). Yu et al. (2003) performed molecular genetic analyses of the 2 groups of adult i, those with and those without congenital cataracts, and performed enzyme function assays and expression patterns for the 3 IGNT transcripts in reticulocytes and lens epithelium cells. They determined that the human I locus expresses 3 IGNT forms, designated IGNTA, IGNTB, and IGNTC, which have different exons 1, but identical exons 2 and 3. IGNTC is the only one of the 3 IGNT transcripts expressed in reticulocytes, whereas only the IGNTB transcript is expressed in lens epithelium cells. Of the 3 IGNT forms, Yu et al. (2003) found that IGNTA and IGNTB were wildtype, but IGNTC was mutant, in adult i whites without congenital cataracts. Whereas only IGNTC was mutant in adult i whites without congenital cataracts, all 3 IGNT forms were mutated in the adult i Taiwanese individuals with congenital cataracts. The results suggested that the human blood group I gene should be reassigned to the IGNTC form rather than the IGNTB form.