Abstract: Objective: To confirm the diagnosis of two cases of autosomal recessive congenital ichthyosis. Methods: Clinical data were collected, and lesional skin biopsies were examined histopathologically. Whole-exome sequencing (WES) was performed on peripheral blood DNA from both probands and their parents. Single-nucleotide variants (SNVs), small insertions/deletions (indels), and copy-number variants (CNVs) were analyzed from the next-generation sequencing (NGS) data. Results: Both probands presented with diffuse, faint erythema and brown, polygonal, adherent scales with sharp borders and overlying white desquamation. Skin histopathology was consistent with ichthyosis. NGS revealed that Proband 1 harbored compound heterozygous variants of the harbored compound heterozygous variants of the PNPLA1 gene: c.106C＞T (p.Arg36Trp) inherited from the father and c.731A＞G (p.Tyr244Cys) inherited from the mother. Proband 2 presented compound heterozygous variants of the PNPLA1 gene: c.1300del (p.Ala434Hisfs*22) inherited from the father and c.731A＞G (p.Tyr244Cys) inherited from the mother. Conclusion: We identified two novel PNPLA1 compound heterozygous genotypes in the gene (c.106C＞T/c.731A＞G and c.1300del/c.731A＞G) thereby expanding the mutational and phenotypic spectra of autosomal recessive congenital ichthyosis.

Key words: autosomal recessive congenital ichthyosis, congenital ichthyosiform erythroderma, PNPLA1 gene, compound heterozygous mutations