In the present study, we present a large cohort of 224 patients affected with ARCI carrying mutations in ALOX12B or ALOXE3. We add 74 novel mutations in ALOX12B and 25 novel mutations in ALOXE3. Furthermore, we investigate the quality and spectrum of mutations, the potential hotspot regions, and the possible correlation of specific mutations with the phenotype. Here, ALOXE3 is linked to autosomal recessive congenital ichthyosis.