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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

Pedigree of the family with autosomal dominant congenital cataract-microcornea syndrome. Squares and circles indicate males and females, respectively, and the black symbols represent the affected members. The asterisks indicate those subjects who underwent clinical and molecular analyses. The arrow indicates the proband.
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f1: Pedigree of the family with autosomal dominant congenital cataract-microcornea syndrome. Squares and circles indicate males and females, respectively, and the black symbols represent the affected members. The asterisks indicate those subjects who underwent clinical and molecular analyses. The arrow indicates the proband.

Mentions: There were five affected individuals in this Chinese family, and three of them (II:6, III:3, and III:5) participated in this study (Figure 1). At the time of this study, all patients had undergone cataract extraction surgeries. Therefore, the clinical findings (summarized in Table 2) were obtained from the medical records. The proband (III:3), a 24-year-old man, was diagnosed with bilateral CCMC at five years of age. The horizontal diameters of his corneas were less than 10 mm. The axial length of his eyes was 25.2 mm oculus dexter (OD) and 24.8 mm oculus sinister (OS), respectively. His mother and sister also showed similar clinical symptoms. Apart from congenital cataract and microcornea, no other eye abnormalities such as microphthalmia, iris coloboma or nystagmus were detected in any of these patients.


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)

Pedigree of the family with autosomal dominant congenital cataract-microcornea syndrome. Squares and circles indicate males and females, respectively, and the black symbols represent the affected members. The asterisks indicate those subjects who underwent clinical and molecular analyses. The arrow indicates the proband.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Pedigree of the family with autosomal dominant congenital cataract-microcornea syndrome. Squares and circles indicate males and females, respectively, and the black symbols represent the affected members. The asterisks indicate those subjects who underwent clinical and molecular analyses. The arrow indicates the proband.
Mentions: There were five affected individuals in this Chinese family, and three of them (II:6, III:3, and III:5) participated in this study (Figure 1). At the time of this study, all patients had undergone cataract extraction surgeries. Therefore, the clinical findings (summarized in Table 2) were obtained from the medical records. The proband (III:3), a 24-year-old man, was diagnosed with bilateral CCMC at five years of age. The horizontal diameters of his corneas were less than 10 mm. The axial length of his eyes was 25.2 mm oculus dexter (OD) and 24.8 mm oculus sinister (OS), respectively. His mother and sister also showed similar clinical symptoms. Apart from congenital cataract and microcornea, no other eye abnormalities such as microphthalmia, iris coloboma or nystagmus were detected in any of these patients.

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