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Y. Li, X. Zhao, Sr., C. Yang, X. Zhang, T. Deng; A Novel MYOC Gene Mutation in a Chinese Family With Juvenile-Onset Open-Angle Glaucoma. Invest. Ophthalmol. Vis. Sci. 2009;50(13):875.
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To report the clinical features and identification of a novel mutation of MYOC gene in a large Chinese family with autosomal dominant juvenile-onset open angle glaucoma (JOAG).
Seventeen family members were examined and medical records were obtained on the remaining two individuals. Clinical ophthalmologic examinations included including slit-lamp inspection, applanation tonometry measurement , gonioscopic examination, optic nerve examination, and Octpus perimeter visual field examination. After informed consent was obtained, peripheral blood samples of all participants were obtained and genomic DNA was extracted. The coding region (exon 1-3), including intron-exon boundary of the MYOC gene, were screened in the family by polymerase chain reaction (PCR) and direct DNA sequencing. Whenever substitutions were identified in a patient, restriction fragment length polymorphism (RFLP) analysis or single strand conformation polymorphism (SSCP) analysis was performed on all available family members and 100 normal controls. To characterize a missense mutation, bioinformatics analysis was performed using the Garnier-Osguthorpe-Robson (GOR) prediction method.
A four generation Chinese family was referred to the Beijing Tongren Hospital. Ten family members were diagnosed JOPG, most of them had extremely high intraocular pressures (IOP) before 30 years old and underwent more than one time trabeculectomies to control the pressure. Six individuals were diagnosed suspected glaucoma due to their IOP greater than 22 mmHg but no characteristic optic disc damage or visual field impairment. Mutation screening of MYOC in this family revealed an A->T transition at position 1348 (p.N450Y) of the cDNA sequence. This missense mutation abolished a HincII restriction site that co-segregated with affected members, the suspect individuals, but was not present in the unaffected members and 100 normal individuals. Compare to the wild type protein, the secondary structure of the mutant p.N450Y MYOC was predicted by GOR method to remove of a coil at the amino acid 447 followed by an addition of a β sheet at amino acid 447. The secondary structure changes may destroy the correct folding of the MYOC.
Early onset JOPG is consistent with a novel mutation in MYOC gene. Our finding expands the mutation spectrum of MYOC and is useful for further genetic consultation and genetic diagnosis.
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