A novel mutation in GJA8 associated with autosomal dominant congenital cataract in a family of Indian origin

Vanita Vanita, Hans Christian Hennies, Daljit Singh, Peter Nürnberg, Karl Sperling, Jai Rup Singh

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Purpose: To identify the genetic defect in an autosomal dominant congenital cataract family, having 15 members in three generations, affected with bilateral cataract that gave the appearance of "full moon" with Y-sutural opacities. Methods: A detailed family history and clinical data were recorded. A genome-wide scan by two point linkage analysis using nearly 400 microsatellite markers in combination with multipoint lod score and haplotype analysis was carried out. Mutation screening was performed in the candidate gene by bidirectional sequencing of amplified products. Results: A maximum two point lod score of 5.45 at θ=0.00 was obtained with marker D1S534. Haplotype analysis placed the cataract locus to a 14.1 cM region between D1S221 and D1S498, in close proximity to the gene for the gap junction channel protein connexin 50 (GJA8) at 1q21. Mutation screening in GJA8 identified a novel G>C transversion at nucleotide position c.235. This nucleotide change resulted in the substitution of highly conserved valine by leucine at codon 79 (V79L). This nucleotide substitution was neither seen in any unaffected member of the family nor in 180 unrelated control subjects (360 chromosomes) from same ethnic background tested by sequence analysis of GJA8. Conclusions: The present study describes the mapping of a locus for congenital cataract that appeared like "full moon" with Y-sutural opacities at 1q21 and identifies a previously unreported mutation in GJA8. These findings thus expand the mutation spectrum of GJA8.

Original languageEnglish
Pages (from-to)1217-1222
Number of pages6
JournalMolecular Vision
Volume12
Publication statusPublished - 18 Oct 2006
Externally publishedYes

Fingerprint

Cataract
Lod Score
Mutation
Nucleotides
Haplotypes
Connexins
Valine
Codon
Leucine
Microsatellite Repeats
Genes
Sequence Analysis
Chromosomes
Genome
Autosomal Dominant Cataract
connexin 50

Cite this

Vanita, V., Hennies, H. C., Singh, D., Nürnberg, P., Sperling, K., & Singh, J. R. (2006). A novel mutation in GJA8 associated with autosomal dominant congenital cataract in a family of Indian origin. Molecular Vision, 12, 1217-1222.
Vanita, Vanita ; Hennies, Hans Christian ; Singh, Daljit ; Nürnberg, Peter ; Sperling, Karl ; Singh, Jai Rup. / A novel mutation in GJA8 associated with autosomal dominant congenital cataract in a family of Indian origin. In: Molecular Vision. 2006 ; Vol. 12. pp. 1217-1222.
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Vanita, V, Hennies, HC, Singh, D, Nürnberg, P, Sperling, K & Singh, JR 2006, 'A novel mutation in GJA8 associated with autosomal dominant congenital cataract in a family of Indian origin', Molecular Vision, vol. 12, pp. 1217-1222.

A novel mutation in GJA8 associated with autosomal dominant congenital cataract in a family of Indian origin. / Vanita, Vanita; Hennies, Hans Christian; Singh, Daljit; Nürnberg, Peter; Sperling, Karl; Singh, Jai Rup.

In: Molecular Vision, Vol. 12, 18.10.2006, p. 1217-1222.

Research output: Contribution to journalArticle

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AU - Vanita, Vanita

AU - Hennies, Hans Christian

AU - Singh, Daljit

AU - Nürnberg, Peter

AU - Sperling, Karl

AU - Singh, Jai Rup

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N2 - Purpose: To identify the genetic defect in an autosomal dominant congenital cataract family, having 15 members in three generations, affected with bilateral cataract that gave the appearance of "full moon" with Y-sutural opacities. Methods: A detailed family history and clinical data were recorded. A genome-wide scan by two point linkage analysis using nearly 400 microsatellite markers in combination with multipoint lod score and haplotype analysis was carried out. Mutation screening was performed in the candidate gene by bidirectional sequencing of amplified products. Results: A maximum two point lod score of 5.45 at θ=0.00 was obtained with marker D1S534. Haplotype analysis placed the cataract locus to a 14.1 cM region between D1S221 and D1S498, in close proximity to the gene for the gap junction channel protein connexin 50 (GJA8) at 1q21. Mutation screening in GJA8 identified a novel G>C transversion at nucleotide position c.235. This nucleotide change resulted in the substitution of highly conserved valine by leucine at codon 79 (V79L). This nucleotide substitution was neither seen in any unaffected member of the family nor in 180 unrelated control subjects (360 chromosomes) from same ethnic background tested by sequence analysis of GJA8. Conclusions: The present study describes the mapping of a locus for congenital cataract that appeared like "full moon" with Y-sutural opacities at 1q21 and identifies a previously unreported mutation in GJA8. These findings thus expand the mutation spectrum of GJA8.

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