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C. Kannabiran, S. P. G. Ponnam, K. Ramesha, S. Tejwani, J. Matalia, B. Ramamurthy; Molecular Genetic Analysis of Congenital Hereditary Cataracts. Invest. Ophthalmol. Vis. Sci. 2008;49(13):449. doi: https://doi.org/.
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To identify genes responsible for hereditary congenital or developmental cataract.
Patients with bilateral congenital or juvenile-onset cataract with no associated developmental, systemic or ocular disorders and their family members were recruited. All subjects underwent detailed ophthalmic evaluation and blood samples were collected for isolation of genomic DNA. . We screened 40 families for mutations in candidate genes including 6 crystallins, 2 connexins, LIM2 (lens intrinsic membrane protein) and the HSF4 (heat shock factor 4) gene byPCR amplification of exons and flanking intronic regions followed by single strand conformation polymorphism analysis and bi-directional sequencing.
Genetic analysis revealed 4 sequence changes in 4 families that are putative pathogenic mutations in the GJA8, GJA3, and LIM2 genes. Two of these changes were homozygous and were found in patients with presumed autosomal recessive disease, and two changes were heterozygous, found in patients with autosomal dominant cataract. Homozygous changes were missense changes of Val196Met in GJA8/Cx50, and Gly154Glu in LIM2/MP19. Heterozygous changes found were Pro199Ser in GJA8/Cx50, and Pro197Ser in GJA3/Cx46. The 4 mutations mentioned, co-segregated with the disease phenotype in each of the families and were absent in 75 unrelated ethnically matched, normal controls. SNPs were also found in various genes.
This study describes novel heterozygous and homozygous mutations in the GJA8 , GJA3 and LIM2 genes leading to congenital cataract. This is the first report of a mutation in LIM2 in association with a phenotype of congenital cataract.
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