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F.L. Munier, W. Ferrini, P. Othenin-Girard, S. Uffer, D.F. Schorderet; Autosomal Dominant Congenital Nuclear Cataract Associated with delG91 in CRYBA3/A1 . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1259.
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Purpose: Linkage and molecular analyses in a large 5-generation family with a congenital nuclear lactescent cataract. Methods: Family history and clinical data were recorded. The phenotype was documented by both slit-lamp and Scheimpflug photography. One lens was evaluated by electron microscopy after cataract extraction. Genotyping was performed using primers from the Applied Biosystems Linkage Mapping Set, version 2. Chromosome panels containing candidate loci related to dominant congenital cataracts, i.e. crystallins, were screened first. Markers were electrophoresed on an ABI-Prism 310 and linkage analysis was performed with MLINK using equal allele frequency and a new mutation rate of 10-4. Primers for the 6 exons of CRYBA3/A1 were designed according to the published sequence and sequencing was done using the Big Dye Terminators. Results: Linkage was observed on chromosome 17 for DNA marker D17S1857 (lod score : 3.44 at theta = 0). Direct sequencing of CRYBA3/A1 which maps to the vicinity revealed an in-frame 3-base deletion in exon 4 (279delGAG). This mutation deleted Glycin-91 and co-segregated in all affected individuals and was never observed in unaffected individuals nor in 250 normal controls from the same ethnic background. Electron microscopy showed abnormal crystal formation with radial appearance. Conclusions: The ΔG91 mutation in CRYBA3/A1 is associated with nuclear lactescent congenital dominant cataract, sparing the sutures. Although mutations in the crystallin genes are not rare, our report is only the second published case of mutation in CRYBA3/A1. The first variant was a splice mutation (IVS3 +1G/A) causing a zonular cataract with sutural opacities (Kannabiran et al., 1998). Our report indicates phenotypic heterogeneity for this gene.
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