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S. Monemi, A. Child, M. Sarfarazi; Is WDR36 a Modifying Gene for Myocilin?. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5592.
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© ARVO (1962-2015); The Authors (2016-present)
We aimed to assess potential modifying effects of the WDR36 gene in primary open angle glaucoma (POAG) families with known Myocilin (MYOC) mutations.
Our previous screening of MYOC gene in 320 unrelated familial and sporadic POAG revealed 11 different disease-causing mutations in a total of 19 cases, 7 with juvenile (JOAG) and 12 with adult-onset POAG. In this study, genomic DNA from the affected subjects of the same families were directly sequenced for 23 coding exons and their immediate intron-exon boundaries of the WDR36 gene.
DNA sequencing of WDR36 in 19 JOAG/POAG cases with prior MYOC mutations revealed a total of 15 intronic or coding DNA variations, including 4 new SNPs. Only one well-documented juvenile-onset Edinburgh family with prior MYOC-Q337R mutation also showed a novel change (P31T) in the WDR36 gene. Although the MYOC-Q337R mutation was present in all of the 5 living affected individuals of this family, only 3 of them had the WDR36-P31T mutation (reported ranges at the time of diagnosis: age of onset 11, 16, 21; IOP: 28-55 mmHg; CDR: 0.3-0.7) and the other 2 affected members (onset: 5, 17; IOP: 32-36; CDR: 0.8-0.9) did not show this change. No consistent clinical differences were observed in the affected subjects with only one (MYOC) or two (MYOC & WDR36) gene mutations. Two unaffected individuals aged 12 and 10 also had the WDR36-P31T mutation but only the younger subject had the MYOC-Q337R mutation. Therefore, presence of WDR36-P31T mutation in this normal subject with MYOC-Q337R may play a minor age-delayed protective effect. None of the other 18 families with either juvenile- or adult-onset POAG showed a significant change in WDR36.
Since only 1 of the 19 unrelated JOAG/POAG individuals had both MYOC and WDR36 mutations and, as there were no co-segregation and/or significant clinical deviations among the affected members with or without 2 gene mutations, it is unlikely that the phenotypic effect of Myocilin mutations are modified by WDR36 gene variations.Supported by EY-009947 and M01RR-06192.
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