WDR36 was first reported in relation to autosomal dominant primary open angle glaucoma G in 2005 (Monemi et al., 2005, PMID: 15677485). The study reported linkage to WDR36 in 7 families with primary open angle glaucoma and identifed four variants that were predicted to be disease causing. However, the variants are not supported by functional evidence -- they are found at relatively high population frequencies in gnomAD.
This gene-disease association has been studied in several case-control studies (PMID: 28658128, 29104481, 22025897, 18172102, 16723468, 19347049, 29540704, 17353431, 28282485, 19875670, 16876519); however, statistical significance was not reached in most. A meta-analysis (Liu et al, 2017; PMID: 28658128) including 5 individual studies reported no statistically significant association of WDR36 variants with primary open angle glaucoma.
WDR36 is expressed ubiquitously, including th eye (PMID: 15677485). The function of WDR36 is not clearly understood, but animal studies suggest a role in eye development. Zebrafish and mouse models show head and eye phenotypes (PMID: 20631153, 18469340); however, they are non-specific and do not support the role of WDR36 variation in glaucoma. With an unclear role for this gene in glaucoma, it is thought to have a modifier effect in disease (PMID: 29104481).
In summary, the evidence supporting the relationship between WDR36 and autosomal dominant primary open angle glaucoma has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role WDR36 plays in glaucoma, but based on the evidence avaialble at this time, the gene is disputed as a monogenic cause of glaucoma.
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