A missense mutation in CRYGD linked with autosomal dominant congenital cataract of aculeiform type.
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.
Department of Human Genetics, Guru Nanak Dev University, Amritsar 143005, Punjab, India. vanita_kumar@yahoo.com
Vanita
V
Vanita
Daljit
D
Singh
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution; D002386:Cataract / Q000235:genetics* / Q000473:pathology; D002648:Child; D025063:Chromosome Disorders / Q000235:genetics* / Q000473:pathology; D003062:Codon; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D038222:gamma-Crystallins / Q000378:metabolism*
C504903:CRYGD protein, human; D003062:Codon; D038222:gamma-Crystallins