Detection of c.139G>A (D47N) mutation in GJA8 gene in an extended family with inheritance of autosomal dominant zonular cataract without pulverulent opacities by exome sequencing.

The aim of this studywas to identify the gene causing bilateral autosomal dominant zonular congenital cataract (ADZCC) without pulverulent opacities in an extended Muslim family by exome sequencing and subsequent analysis. An extended family of 37 members (14 affected and 23 unaffected) who belong to different nuclear families was screened for causative gene. Proband and her unaffected son were screened for causative variant by exome sequencing followed by Sanger sequencing of the proband's entire nuclear family. The rest of the members were further screened for variants detected, by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and tetra-primer amplification refractorymutation system-polymerase chain reaction (T-ARMS PCR). Review of exome sequencing data of the proband and her unaffected son for 40 known genes causing congenital nonsyndromic cataracts revealed two variants, namely c.139G>A (p.Asp47Asn; D47N) in the GJA8 gene and c.2036C>T in the FYCO1 gene to be potentially pathogenic. Further, validation of these two variants in the entire family showed cosegregation of c.139G>A variant in GJA8 with ADZCC without pulverulent opacities. Variation of c.2036C>T in FYCO1 was not associated with disease in the family. The mutation c.139G>A in the GJA8 gene detected in the present study was also previously reported in Caucasian and Chinese families but with different phenotypes, i.e. nuclear and nuclear pulverulent cataracts. Thus, the mutation c.139G>A in GJA8 appears to exhibit marked interfamilial phenotypic variability.

Association of IFN-g+874(T/A) polymorphism with female patients of age-related cataracts.

AIM: Exposure to UV light is the major risk factor in the development of age-related cataract (ARC). UV filters produced during tryptophan catabolism maintain the transparency of the lens and protect retina from photo damage. Indoleamine 2, 3-dioxygenase (IDO), the first rate-limiting enzyme in the tryptophan catabolism, is up regulated by interferon-gamma (IFN-g) which harbors single nucleotide polymorphisms (SNPs). The T allele of SNP at +874 position of the IFN-g is known to be associated with the up regulation of IDO than the allele A. Hence, we attempted to study the IFN-g+874(T/A) polymorphism for its association with ARCs. MATERIALS AND METHODS: A total of 680 cataract cases [199 nuclear (NC), 175 cortical (CC), 174 posterior subcapsular (PSC), and 132 mixed types (MT)] and 210 healthy controls were genotyped for +874(T/A) polymorphism using amplification refractory mutation system-polymerase chain reaction on 2% agarose gel stained with ethidium bromide. RESULTS: There was increased risk for CC and PSC when the patients happened to be females, with low body mass index and with early onset. Considering the IFN-g polymorphism, a high risk was observed for CC and PSC in female patients of AA genotype with significant protection for those with TT genotypes. CONCLUSION: Present results indicate that +874(T/A) polymorphism may be considered as one of the biomarkers to distinguish between the CC and PSC types of cataracts for risk estimations. The study appears to be the first of its kind reporting an association of IFN-g+874(T/A) polymorphism with ARCs.