Phenotypic spectrum of autosomal recessive congenital ichthyosis due to PNPLA1 mutation

Funding sources: this work was supported by NIH/NIAMS R01 AR068392 and the Yale Center for Mendelian Genomics (U54 HG006504). Conflicts of interest: none declared. Dear Editor, The ichthyoses are rare skin disorders linked by the common finding of scale and concomitant barrier function abnormalities. Recently, mutations in PNPLA1, which encodes patatin‐like phospholipase domain containing 1 and plays a role in the formation of the epidermal lipid barrier, have been identified as a rare cause of nonsyndromic autosomal recessive congenital ichthyosis (ARCI).1,2,3,4,5,6,7 We identified patients with PNPLA1 mutations within our registry of 732 ichthyosis kindreds. DNA was isolated from blood, and either multiplex targeted next‐generation sequencing of 42 genes known to cause disorders of keratinization, or whole‐exome sequencing was performed (Appendix S1; see Supporting Information). Fourteen unrelated probands with ARCI were found to be compound heterozygous or homozygous for mutations in PNPLA1,which were confirmed with Sanger sequencing. PNPLA1 mutations segregated with disease in all kindreds, five of which were consanguineous (Figs S1–14; see Supporting Information).