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A novel mutation in GJA8 causing congenital cataract-microcornea syndrome in a Chinese pedigree.

Hu S, Wang B, Zhou Z, Zhou G, Wang J, Ma X, Qi Y - Mol. Vis. (2010)

Bottom Line: This mutation was responsible for the familial disorder through the substitution of a highly conserved arginine to tryptophan at codon 198 (p.R198W).This report is the first to relate p.R198W mutation in GJA8 with CCMC.The result expands the mutation spectrum of GJA8 in associated with congenital cataract and microcornea, and implies that this gene has direct involvement with the development of the lens as well as the other anterior segment of the eye.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

ABSTRACT

Purpose: To identify the underlying genetic defect in a four-generation family of Chinese origin with autosomal dominant congenital cataract-microcornea syndrome (CCMC).

Methods: All individuals in the study underwent a full clinical examination and the details of history were collected . Genomic DNA extracted from peripheral blood was amplified by polymerase chain reaction (PCR) method and the exons of all candidate genes were sequenced.

Results: Direct sequencing of the encoding regions of the candidate genes revealed a heterozygous mutation c.592C-->T in exon 2 of the gap junction protein, alpha 8 (GJA8) gene. This mutation was responsible for the familial disorder through the substitution of a highly conserved arginine to tryptophan at codon 198 (p.R198W). This change co-segregated with all affected members of the family, but was not detected either in the non-carrier relatives or in the 100 normal controls.

Conclusions: This report is the first to relate p.R198W mutation in GJA8 with CCMC. The result expands the mutation spectrum of GJA8 in associated with congenital cataract and microcornea, and implies that this gene has direct involvement with the development of the lens as well as the other anterior segment of the eye.

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Related in: MedlinePlus

Mutation analysis of GJA8. A: Partial nucleotide sequence of GJA8 from an affected individual. The sequence in affected individuals showed a heterozygous C→T transversion (indicated by the arrow), resulting in a substitution of arginine for tryptophan at amino acid residue 198. B: Unaffected individuals and the control subjects lacked this nucleotide change. C: The alignment of the GJA8 sequence with the corresponding segments in diverse species was shown. The 198th arginine was highly conserved in connexin 50 proteins from several species.
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f2: Mutation analysis of GJA8. A: Partial nucleotide sequence of GJA8 from an affected individual. The sequence in affected individuals showed a heterozygous C→T transversion (indicated by the arrow), resulting in a substitution of arginine for tryptophan at amino acid residue 198. B: Unaffected individuals and the control subjects lacked this nucleotide change. C: The alignment of the GJA8 sequence with the corresponding segments in diverse species was shown. The 198th arginine was highly conserved in connexin 50 proteins from several species.

Mentions: In all affected individuals, bidirectional sequencing of the coding regions of the candidate genes revealed a heterozygous missense mutation, C→T, at nucleotide 592 in exon 2 of GJA8 (Figure 2A). This mutation resulted in the replacement of a highly conserved arginine by tryptophan (Figure 2C). This change co-segregated with the affected members of the family, but was not detected in either non-carrier relatives or 100 normal controls (Figure 2B). No other mutations were found except for the non-pathogenic SNPs.


A novel mutation in GJA8 causing congenital cataract-microcornea syndrome in a Chinese pedigree.

Hu S, Wang B, Zhou Z, Zhou G, Wang J, Ma X, Qi Y - Mol. Vis. (2010)

Mutation analysis of GJA8. A: Partial nucleotide sequence of GJA8 from an affected individual. The sequence in affected individuals showed a heterozygous C→T transversion (indicated by the arrow), resulting in a substitution of arginine for tryptophan at amino acid residue 198. B: Unaffected individuals and the control subjects lacked this nucleotide change. C: The alignment of the GJA8 sequence with the corresponding segments in diverse species was shown. The 198th arginine was highly conserved in connexin 50 proteins from several species.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2927419&req=5

f2: Mutation analysis of GJA8. A: Partial nucleotide sequence of GJA8 from an affected individual. The sequence in affected individuals showed a heterozygous C→T transversion (indicated by the arrow), resulting in a substitution of arginine for tryptophan at amino acid residue 198. B: Unaffected individuals and the control subjects lacked this nucleotide change. C: The alignment of the GJA8 sequence with the corresponding segments in diverse species was shown. The 198th arginine was highly conserved in connexin 50 proteins from several species.
Mentions: In all affected individuals, bidirectional sequencing of the coding regions of the candidate genes revealed a heterozygous missense mutation, C→T, at nucleotide 592 in exon 2 of GJA8 (Figure 2A). This mutation resulted in the replacement of a highly conserved arginine by tryptophan (Figure 2C). This change co-segregated with the affected members of the family, but was not detected in either non-carrier relatives or 100 normal controls (Figure 2B). No other mutations were found except for the non-pathogenic SNPs.

Bottom Line: This mutation was responsible for the familial disorder through the substitution of a highly conserved arginine to tryptophan at codon 198 (p.R198W).This report is the first to relate p.R198W mutation in GJA8 with CCMC.The result expands the mutation spectrum of GJA8 in associated with congenital cataract and microcornea, and implies that this gene has direct involvement with the development of the lens as well as the other anterior segment of the eye.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

ABSTRACT

Purpose: To identify the underlying genetic defect in a four-generation family of Chinese origin with autosomal dominant congenital cataract-microcornea syndrome (CCMC).

Methods: All individuals in the study underwent a full clinical examination and the details of history were collected . Genomic DNA extracted from peripheral blood was amplified by polymerase chain reaction (PCR) method and the exons of all candidate genes were sequenced.

Results: Direct sequencing of the encoding regions of the candidate genes revealed a heterozygous mutation c.592C-->T in exon 2 of the gap junction protein, alpha 8 (GJA8) gene. This mutation was responsible for the familial disorder through the substitution of a highly conserved arginine to tryptophan at codon 198 (p.R198W). This change co-segregated with all affected members of the family, but was not detected either in the non-carrier relatives or in the 100 normal controls.

Conclusions: This report is the first to relate p.R198W mutation in GJA8 with CCMC. The result expands the mutation spectrum of GJA8 in associated with congenital cataract and microcornea, and implies that this gene has direct involvement with the development of the lens as well as the other anterior segment of the eye.

Show MeSH
Related in: MedlinePlus