1. Genetic Heterogeneity in Autosomal Recessive Congenital Cataracts in Persian Jews David Zadok, Yaakov Goldich, Isaac Avni, David Varssano, Vladimir Rozitsky, Eran Pras Assaf Harofeh Medical Center, Zerifin, Israel Authors have no financial interest

2. PURPOSE: To identify the genetic defect associated with autosomal recessive congenital cataract (ARCC) in three consanguineous families of Persian Jewish origin. METHODS: Patients were examined, blood samples were collected, DNA was isolated and I/i blood typing was tested. Mutation analysis of the Glucosaminyl N-acetyl Transferase-2 (GCNT2) and Crystallin Alpha-A (CRYAA) genes was performed by direct sequencing of PCR-amplified exons. Results: A previously reported CRYAA gene mutation (W9X) was found in two of the families, but not in the other. In the third family the rare blood type- “i” was found in affected family members. Consequent sequencing of the GCNT2 gene have identified a novel mutation G312D. Conclusion: Genetic heterogeneity was observed within Persian Jewish families affected by ARCC. The associated mutations include W9X of the CRYAA gene, and a novel mutation G312D in the GCNT2 gene.

3. Jewish Persian Congenital Cataract Families Congenital cataract and “II” (normal) blood group Congenital cataract and “ii” blood group Family 1Family 2 Family 3

4. Family 1 and 2 Sequence chromatograms from a normal control subject (top) and a patient (bottom). A G → A change in the patient resulted in a premature stop codon (TGA). A nonsense mutation (W9X) in CRYAA causes autosomal recessive cataract in an inbred Jewish Persian family. Pras E, et al. Invest Ophthalmol Vis Sci. 2000;41:3511-5

5. Blood type “ii” + Congenital Cataract in Persian Jews Family 3 Sequence chromatograms of the GCNT2 (IGNT) gene from a normal control subject (top) and a patient (bottom). A G → A substitution in the patients results in the formation of a novel missense mutation G312D (a change of Glycine to Aspartic acid).

7. Conclusion Genetic heterogeneity was observed within Persian Jewish families affected by ARCC. The associated mutations include W9X of the CRYAA gene, and a novel mutation G312D in the GCTN2 gene.