Purpose. Studies involving genotyping of STR markers at 2q34 have repeatedly found the region to host the disease haplotype for pediatric cataract. Present study investigated the association of D2S2944 marker, in sperm associated antigen 16 (SPAG16) gene and rs2289917 polymorphism, in γ-crystallin B gene, with childhood cataract. Methods. 97 pediatric cataract cases and 110 children with no ocular defects were examined for tetranucleotide repeat marker/SNP using PCR-SSLP/RFLP techniques. Polymorphisms were assessed for association using contingency tables and linkage disequilibrium among alleles of the markers was estimated. Energy-optimization program predicted the secondary structure models of repeats of D2S2944. Results. Seven alleles of D2S2944, with 9–15 “GATA” repeats, were observed. Frequency of the longer allele of D2S2944, ≥(GATA)13 repeats, was 0.73 in cases and 0.56 in controls ( ). Male children bearing ≥(GATA)13 repeats showed >3-fold higher risk for cataract (CI95% = 1.43–7.00, , ) as compared to female children ( , CI95% = 0.49–2.92, ). Cases with haplotype—≥(GATA)13 of D2S2944 and “C” allele rs2289917—have a higher risk for pediatric cataract ( , CI95% = 1.595~5.463, ). >(GATA)13 repeats formed energetically more favorable stem-loop structure. Conclusion. Intragenic microsatellite repeat expansion in SPAG16 gene increases predisposition to pediatric cataract by probably interfering posttranscriptional events and affecting the expression of adjacent lens transparency gene/s in a gender bias manner. 1. Introduction Cataract is a major cause of treatable childhood blindness, with a prevalence of around 5 to 15 cases per 10,000 children in India [1]. Cataract in children is particularly serious because it has the potential for inhibiting visual development, resulting in permanent blindness and disability. Inherited cataracts represent 8–25% of infantile cataract cases [2]. Understanding the genetics of cataract will not only lead to better treatment approaches but also open avenues for effective counseling. Most inherited cataracts mapped on to chromosome 2 are associated with a subgroup of genes, namely, gamma-crystallins (CRYG) present at 2q33–35, encoding proteins important for maintenance of lens transparency and homeostasis [3]. The chromosomal region from 198？Mb to 220？Mb on chromosome 2q has been repeatedly found to host the disease haplotype for pediatric cataract [4]. Infact Cat-Map database summary shows that major portion of mutations/variations observed to be associated with cataracts in this region have been reported in Asians
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