Variants in KLF4 affecting residue Asp441 cause an autosomal dominant syndromic ichthyosis

Loss-of-function variants affecting residue Asp441 of KLF4 cause an autosomal dominant syndromic ichthyosis with multiorgan involvement. These variants impair KLF4 transcriptional activity, leading to the downregulation of multiple genes, particularly KLK7 and WNT10A. This may disrupt the skin desquamation process and affect multiorgan development in the patients.