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Susan Williams, Tasha Wainstein, Trevor Carmichael, Michele Ramsay; MYOC Variants In POAG In Black South Africans. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6220.
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© ARVO (1962-2015); The Authors (2016-present)
Mutations in the MYOC gene are important as causal factors in some forms of POAG. Sequencing of the MYOC gene in black South Africans previously identified 3 potentially pathogenic mutations. The aim of this study was to examine the role of these mutations in the etiology of POAG in this population.
The mutations are listed in Table 1. They were genotyped in 215 black South African POAG patients and 214 controls using the Illumina BeadXpress genotyping platform. Family members of participants identified with the mutations were counseled and screened for glaucoma with a clinical examination. Sanger sequencing was used for mutation detection.
The results of the BeadXpress genotyping and the mutation screening are listed in Table 1. None of the relatives screened for Gly374Val had the mutation or POAG. A sibling of a similar age to the Lys500Arg index case carried the mutation but had no evidence of POAG whereas the index case’s daughter was a POAG suspect but did not carry the mutation. Of the 4 relatives that were carriers of the Tyr453del mutation, 1 was diagnosed with POAG and 1 was a POAG suspect. The 19 year old daughter of a POAG patient and the 38 year old son of an unaffected control did not have POAG but carried the mutation. In this small sample, the penetrance of this mutation was 25% at 50 years and 75% at 70 years. POAG patients with the mutation have adult-onset POAG with high intraocular pressures and advanced cupping (Table 2).
Black South Africans with POAG may have a MYOC mutation that either causes or contributes to their risk for developing POAG in approximately 3.3%. The commonest mutation is a frameshift mutation (Tyr453del) that is incompletely penetrant. It is likely that the mutation causes gain-of-function due to a truncated protein. That the mutation is necessary but insufficient introduces a counseling dilemma. Mutation screening can, however, identify high-risk individuals who can be monitored to detect early signs of the disease. The Gly374Val mutation is predicted to be damaging to MYOC. It is an uncommon cause of POAG in this population. The Lys500Arg mutation is predicted to be benign and tolerated. In the family with the mutation, it did not segregate with the disease suggesting that it is a neutral polymorphism. This study has important implications for the management and counseling of black South African patients with POAG and their families.
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