The human knockout phenotype of PADI6 is female sterility caused by cleavage failure of their fertilized eggs.

To the Editor: Naturally occurring human knockouts have greatly expanded our understanding of the medical relevance of genes, or lack thereof (1). Indeed, while biallelic inactivation of genes can result in severe Mendelian disorders, other genes seem to be toleratedwhen knocked out (2). We have been studying embryonic lethality as an extreme Mendelian phenotypic consequence of human knockout events by taking advantage of the consanguineous nature of the Saudi population where autozygosity facilitates the homozygous occurrence of alleles, including inactivating ones. We have previously shown an example of very early embryonic lethality caused by failure of homozygously TLE6 inactivated eggs to undergo the first cleavage after fertilization (3). In this communication, we report the identification of a very similar phenotype caused by PADI6 homozygous inactivation.