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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

The predicted secondary structures of the wild-type and the mutant-type GJA8 sequences. The predicted secondary structures of the wild-type GJA8 sequence (A) and the mutant-type sequence (B) are shown. The target sequences are labeled by red, which indicate that there is a turn in the wild type replaced by a helix in the mutant type.
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f4: The predicted secondary structures of the wild-type and the mutant-type GJA8 sequences. The predicted secondary structures of the wild-type GJA8 sequence (A) and the mutant-type sequence (B) are shown. The target sequences are labeled by red, which indicate that there is a turn in the wild type replaced by a helix in the mutant type.

Mentions: After input the amino acid sequences of the wild-type GJA8 protein and the mutant, the PSIC score from Polyphen analysis was 3.149, which meant that the variant (p.R198W) was predicted as being “probably damaging” with high confidence. In comparison with the wild-type GJA8 protein, the hydrophobicity of the mutant was dramatically increased (Figure 3). The secondary structure prediction suggested that the mutation R198W led to a turn replaced by a helix. (Figure 4).


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)

The predicted secondary structures of the wild-type and the mutant-type GJA8 sequences. The predicted secondary structures of the wild-type GJA8 sequence (A) and the mutant-type sequence (B) are shown. The target sequences are labeled by red, which indicate that there is a turn in the wild type replaced by a helix in the mutant type.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: The predicted secondary structures of the wild-type and the mutant-type GJA8 sequences. The predicted secondary structures of the wild-type GJA8 sequence (A) and the mutant-type sequence (B) are shown. The target sequences are labeled by red, which indicate that there is a turn in the wild type replaced by a helix in the mutant type.
Mentions: After input the amino acid sequences of the wild-type GJA8 protein and the mutant, the PSIC score from Polyphen analysis was 3.149, which meant that the variant (p.R198W) was predicted as being “probably damaging” with high confidence. In comparison with the wild-type GJA8 protein, the hydrophobicity of the mutant was dramatically increased (Figure 3). The secondary structure prediction suggested that the mutation R198W led to a turn replaced by a helix. (Figure 4).

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