TGM1 and hemorrhagic disease: From classical clinical and genetic studies it has been known that humans with knock out, homozygous LOF transglutaminase genes with disease phenotype in the case of F13a (bleeding disorder, prevalence 1 in 2 millions) [60, 61, 62, 77, 78], TGM1 (lamellar ichthyosis, prevalence 1 in 150 thousands) [63, 64], and TGM5 (acral peeling skin, prevalence <1 in 1 million) [65, 66, 67] deficiencies.