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J. Graw, N. Klopp, T. Illig, W. Schmidt; Two Gja8 Mutations: An Insertion Causing a Recessive Triangular Cataract, and a Rare Polymorphism. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4072. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Aim of the study was the characterization of underlying mutations in two cataract families.
Families suffering from congenital cataracts have been collected in Gießen (Germany). Lens material from surgeries was collected, immediately frozen at -80oC and used for cDNA production. Blood was taken from the probands and available family members. PCR amplified DNA fragments were characterized by sequencing and restriction digest.
The proband LB suffers from a diffuse white lens opacity; the parents are healthy. In the cDNA coding for GJA8, a T741->G nucleotide substitution was observed (I247M amino-acid exchange); this mutation was reported previously to be causative for cataracts. Surprisingly, the same mutation was identified in the healthy mother suggesting that it has no full penetrance or is even a rather rare polymorphism than a cataract-causing mutation.The proband AD suffers from a dense, triangular nuclear cataract. The parents are consanguineous and the mother and grandmother suffer from a discrete, symmetric opacity of the fetal lens nucleus. In the proband’s lens cDNA of GJA8, a homozygous insertion of one G was observed after pos. 776 leading to a frame shift and 123 novel amino acids. The homozygous mutation was confirmed in the genomic DNA and also present in the cataract-operated brother of the proband; all other family members investigated were heterozygous. The mutation could not be detected in 96 healthy controls from Germany.
While the I247M mutation is most likely a rare polymorphism or is not fully penetrant, the ins776G mutation causes a recessive triangular cataract with variable expressivity of a weak phenotype in heterozygotes.
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