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A novel truncation mutation in GJA1 associated with open angle glaucoma and microcornea in a large Chinese family.

ABSTRACT: To identify genetic defects in a large family with open angle glaucoma (OAG) and microcornea.Genomic DNA was prepared from leukocytes of 15 individuals from three generations of a Chinese family, including seven individuals with OAG and microcornea, one with microcornea alone, and seven healthy individuals. Whole exome sequencing was performed on genomic DNA of the proband. Candidate variants were obtained through multiple steps of bioinformatics analysis and validated by Sanger sequencing and segregation analysis.Exome sequencing detected a candidate variant in GJA1, a novel truncation mutation (c.791_792delAA, p.K264Ifs*43). This mutation was present in all seven individuals with OAG and microcornea and the individual with microcornea alone, but not in the seven unaffected relatives in the family. It was not present in 1394 alleles from 505 unrelated controls without glaucoma and 192 normal controls. Extraocular signs were not observed in seven out of the eight individuals; only one was affected with dental enamel hypoplasia and syndactyly.A novel truncation mutation in GJA1 is associated with OAG and microcornea in a Chinese family. This suggests that GJA1 should be included as a candidate gene for glaucoma.

SUBMITTER: Huang X

PROVIDER: S-EPMC4506350 | biostudies-other | 2015 Jul

REPOSITORIES: biostudies-other

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A novel truncation mutation in GJA1 associated with open angle glaucoma and microcornea in a large Chinese family.

Huang X X Wang N N Xiao X X Li S S Zhang Q Q

Eye (London, England) 20150515 7

<h4>Purpose</h4>To identify genetic defects in a large family with open angle glaucoma (OAG) and microcornea.<h4>Methods</h4>Genomic DNA was prepared from leukocytes of 15 individuals from three generations of a Chinese family, including seven individuals with OAG and microcornea, one with microcornea alone, and seven healthy individuals. Whole exome sequencing was performed on genomic DNA of the proband. Candidate variants were obtained through multiple steps of bioinformatics analysis and vali ...[more]

PMID: 25976645

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Project description:PurposeGlaucoma is the leading cause of irreversible blindness worldwide. Most of the cases are primary open angle glaucoma (POAG). POAG is a genetically heterogenous disease; autosomal dominance is the most frequent type of monogenic inheritance. In this study, we identified the genotype of a MYOC mutation and investigated the phenotype of a Chinese juvenile-onset open angle glaucoma (JOAG) pedigree (GZ.1 pedigree).MethodsBlood samples were obtained from 24 participants. We performed sequence and gene linkage analysis in the GZ.1 pedigree retrospectively. Comprehensive ophthalmologic examinations were performed for each family member. Pharmacological treatment or filtering surgery was performed as needed according to the intraocular pressure (IOP) of each individual.ResultsA Pro370Leu myocilin mutation located in exon 3 of MYOC was identified in 24 members of the GZ.1 pedigree. Sixteen patients had juvenile-onset primary open-angle glaucoma (JOAG), and the others participating in the project had no such genotype. Analysis of polymorphic microsatellite markers indicated that the disease in GZ.1 is autosomal dominant inheritance. The patients in GZ.1 are characterized by early age of onset (before 35 years of age), severe clinical presentations, and high intraocular pressure unresponsive to pharmacological treatment; requiring 89.5% of the patients to undergo filtering surgery. Fortunately, the success rate of surgery was high. None of the patients required further medical treatment and only one demonstrated low IOP fundus changes.ConclusionsThis is the first evidence of a founder effect for a Pro370Leu myocilin mutation in a Chinese POAG pedigree. The family with the Pro370Leu myocilin mutation presents with juvenile-onset glaucoma. After 10 years of follow-up, it is evident that the mutation is closely associated with the phenotype of the patients. Analysis of MYOC in JOAG patients may enable the identification of at-risk individuals and help prevent disease progression toward the degeneration of the optic nerve, and may also contribute to genetic counseling.

Dataset Information

A novel truncation mutation in GJA1 associated with open angle glaucoma and microcornea in a large Chinese family.

Publications

A novel truncation mutation in GJA1 associated with open angle glaucoma and microcornea in a large Chinese family.

Similar Datasets

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