Purpose: To identify the genetic defect associated with autosomal recessive congenital cataract in four Arab families from Israel.
Methods: Genotyping was performed using microsatellite markers spaced at approximately 10 cM intervals. Two-point lod scores were calculated using MLINK of the LINKAGE program package. Mutation analysis of the glucosaminyl (N-acetyl) transferase 2 gene (GCNT2) gene was performed by direct sequencing of PCR-amplified exons.
Results: The cataract locus was mapped to a 13.0-cM interval between D6S470 and D6S289 on Chr. 6p24. A maximum two-point lod score of 8.75 at theta = 0.019 was obtained with marker D6S470. Sequencing exons of the GCNT2 gene, mutations of which have been associated with cataracts and the i blood group phenotype, revealed in these families a homozygous G-->A substitution in base 58 of exon-2, resulting in the formation of premature stop codons W328X, W326X, and W328X, of the GCNT2A, -B, and -C isoforms, respectively. Subsequent blood typing of affected family members confirmed the possession of the rare adult i blood group phenotype.
Conclusions: A nonsense mutation in the GCNT2 gene isoforms is associated with autosomal recessive congenital cataract in four distantly related Arab families from Israel. These findings provide further insight into the dual role of the I-branching GCNT2 gene in the lens and in reticulocytes.