To detect the underlying genetic defects in two autosomal dominant congenital
cataract (ADCC) families, having respectively twenty and four members affected with bilateral congenital
cataract. Detailed family history and clinical data were recorded. Mutation screening in twenty three candidate genes including
crystallins (CRYAA, CRYAB, CRYBA1/A3, CRYBA2, CRYBA4, CRYBB1, CRYBB2, CRYBB3, CRYGA, CRYGB, CRYGC, CRYGD, and CRYGS), gap junctional channels;
connexins (GJA8, GJA3), beaded filament chain
proteins (BFSP1, BFSP2), major intrinsic
protein (MIP), lens intrinsic membrane protein-2 (LIM2), transcriptional factor (MAF), and in genes encoding for
membrane-associated proteins (TMEM114, CHMP4B, EPHA2) was performed by bi-directional sequence analysis of the amplified products. In family A twenty members in six generations were affected by bilateral aculeiform type
cataract and in family B four affected members in three generations had granular nuclear
cataract. Mutation screening in already known candidate genes by sequence analyses revealed
proline to
threonine substitution at
codon 23 (p.Pro23Thr) in CRYGD for aculeiform type
cataract in family A. The family B with four members affected by granular nuclear
cataract, however, could not be linked with any of these analyzed 23 candidate genes. The present study describes identification of p.Pro23Thr mutation in CRYGD for aculeiform type
cataract in an ADCC family of Indian origin. The identical mutation has previously been reported to be linked with different phenotypes; lamellar
cataract,
cerulean cataract, coralliform
cataract, flaky
silica-like nuclear
cataract and fasciculiform type
cataract in different ADCC families. Interestingly, a mutation of different
codon, i.e., p.Arg58His in CRYGD has been reported to be linked with aculeiform
cataract in four different families; two from Switzerland, one from Macedonia and in a Mexican family. The findings in present study thus expand the genetic heterogeneity for aculeiform type
cataract. Further, exclusion of these twenty three known candidate genes in family B having ADCC of granular nuclear type indicates the role of some other gene apart from for
crystallins, gap junction channels, beaded filaments and
membrane-associated proteins, and MAF for this phenotype.