Novel and known MYOC exon 3 mutations in an admixed Peruvian primary open-angle glaucoma population - PubMed (original) (raw)

Novel and known MYOC exon 3 mutations in an admixed Peruvian primary open-angle glaucoma population

Veronica Mendoza-Reinoso et al. Mol Vis. 2012.

Abstract

Purpose: The aim of this study was to characterize a representative sample of the Peruvian population suffering open-angle glaucoma (OAG) with respect to the myocilin gene (MYOC) mutations, glaucoma phenotype, and ancestry for future glaucoma risk assessment.

Methods: DNA samples from 414 unrelated Peruvian subjects, including 205 open-angle glaucoma cases (10 juvenile glaucoma [JOAG], 19 normal-tension glaucoma [NTG], and 176 POAG) and 209 randomly sampled controls, were screened for nucleotide changes in MYOC exon 3 by conformational sensitive gel electrophoresis (CSGE) and mutation screening.

Results: We identified a probable causative novel MYOC missense mutation, Gly326Ser, in one POAG case and found a consistent genotype-phenotype correlation in eight of his relatives. We also found the known causative MYOC mutation Trp286Arg in one JOAG case and one POAG case. A known causative single base MYOC deletion, T1357, was found in one POAG case. Two previously reported silent polymorphisms, Thr325Thr and Tyr347Tyr, were found in both the case and the control populations. A novel missense variant, Met476Arg, was identified in two unrelated controls.

Conclusions: The screening of exon 3 of MYOC in a representative sample of 205 independent POAG patients from Peru and 209 matched controls identified novel and previously reported mutations (both pathogenic and nonpathogenic) from other global regions. These results reflect the complex admixture of Amerindian and Old World ancestry in urban populations of Latin America, in general, and in Peru, in particular. It will be important to gather information about the ancestral origin of MYOC and other POAG gene mutations to develop screening panels and risk assessment for POAG in Peru.

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Figures

Figure 1

Figure 1

Novel mutation Gly326Ser caused by a transition G→A in nucleotide MYOC 976 changing codon GGT (Gly) to AGT (Ser). Found in case G62 and two of his first and second degree POAG affected relatives plus a younger relative with OHT.

Figure 2

Figure 2

OHT and POAG family with MYOC Gly326Ser mutation and age of onset. The variant was detected in proband (P, case G62) and an extended analysis was performed in his closer relatives. Sister 01A with POAG, niece 03A has OHT with tendency to angle closure, and first cousin 24A with POAG are heterozygous for Gly326Ser. Cousin 05A has pseudoexfoliative glaucoma. Cousin 08A has been diagnosed with POAG. The three first cousins are heterozygous for MYOC Thr325Thr.

Figure 3

Figure 3

Novel polymorphism Met476Arg caused by a T→G transversion in nucleotide MYOC 1427 and the codon 476 from Met to Arg. This variant was found in 2 normal controls with neither glaucoma nor high IOP.

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