Presence of myocilin sequence variants in Japanese patients with open-angle glaucoma - PubMed (original) (raw)

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Presence of myocilin sequence variants in Japanese patients with open-angle glaucoma

MingGe Mengkegale et al. Mol Vis. 2008.

Abstract

Purpose: To examine the myocilin (MYOC) gene for mutations in Japanese patients with primary open-angle glaucoma (POAG) and to determine the phenotypes of the patients with the mutations.

Methods: One-hundred thirty-eight unrelated Japanese patients with POAG were studied. Genomic DNA was extracted from leukocytes of peripheral blood, and the three coding exons including the intron-exon boundaries were amplified by polymerase chain reaction (PCR) and directly sequenced bi-directionally.

Results: Two sequence variants were identified, one novel non-synonymous amino acid change (p.Gln297His) and one reported synonymous amino acid change (p.Ala363Thr). These mutations were not detected in the 118 ethnically-matched controls. p.Gln297His was found in a 70-year-old man, who developed POAG at a late age, and his intraocular pressure was high. p.Ala363Thr was found in two cases, and both patients developed POAG at an early age and had high intraocular pressures that responded poorly to medical treatment.

Conclusions: Two non-synonymous variants, p.Gln297His and p.Ala363Thr, indicate that they are involved in the pathogenesis of POAG. p.Ala363Thr has been found in another Japanese population and would be useful in genetic testing.

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Figures

Figure 1

Figure 1

Pedigree of Case 2. Solid squares indicate the affected men, and solid circles indicate the affected women. An arrow points to the proband. The gray square indicates the ocular hypertension and glaucoma suspect. The family included six affected individuals.

Figure 2

Figure 2

Pedigree of Case 3. Solid circles indicate the proband and affected mother, and the solid square indicates the affected brother. The white square indicates the father, who is an unaffected subject.

Figure 3

Figure 3

Multiple amino acid alignments and evolutionary conservation of p.Gln297 and p.Arg363 of MYOC variants. Protein domains of MYOC are shown. Gln297 and Arg363 (underlined) are conserved among five species, humans, chimpanzees, rats, mice, and dogs.

Figure 4

Figure 4

Mutation spectrum found in Japanese individuals. The black boxes indicate the three exons. Nine out of 11 mutations are located in exon 3, the olfactomedin-like domain. The two underlined mutations were found in this study.

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