Mutation rate estimates are not compatible with autosomal dominant inheritance of the dysplastic nevus “syndrome”

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Abstract
Dysplastic nevi represent precursor lesions harboring an increased risk of evolving into melanoma. Their association with familial melanoma is usually considered a monogenic syndrome with autosomal dominant transmission. To test this concept we estimated the mutation rates. When derived directly from the sporadic occurrence of the trait, the mutation rate is exceedingly high (0.9%–2.5%), whereas, as estimated with the aid of Haldane's formula it would be 0.007% to 0.02%. Accordingly, newly arising mutation would out‐number eliminated mutations by 100:1. Even if only 80% of all old mutations are passed onto the next generation, this ratio of 100:1 would rapidly change. After only a few generations, 10% of the world population should be affected with the dysplastic nevus “syndrome”. The apparent lack of a genetic equilibrium between newly arising and eliminated mutations is not compatible with autosomal dominant inheritance of the dysplastic nevus “syndrome”.