Heterozygous and homozygous carriers of BMP15 mutations. Shown are the different effect of mutation: A, In C320Y heterozygosity, the BMP15 gene is expressed as wild-type (WT) (50%) and mutant (50%). Only the WT dimerizes with GDF9 to produce cumulin, which can bind to the receptor, and exerts all activity (100%). The mutant cannot dimerize, cannot bind to the receptor, and exerts no effect on the receptor (0%). B, In R329H heterozygosity, the BMP15 gene is expressed as WT (50%) and mutant (50%). Both the WT and the mutant can dimerize into cumulin, and bind to the receptor. WT cumulin (50%) is a receptor agonist, whereas mutant cumulin (50%) is an antagonist, and their combination reduces receptor activity. C, In C320Y homozygosity, the BMP15 gene is expressed as mutant only (100%). The mutant cannot dimerize, cannot bind to the receptor, and exerts no effect on the receptor (0%). D, In R329H homozygosity, the BMP15 gene is expressed as mutant only (100%). The mutant dimerizes into a cumulin antagonist and can bind to the receptor. However, the antagonist does not activate the receptor (0%).