408 POFUT1 mutation in a patient with flexural and acral hyperpigmented reticulated macules

Abstract

Background: Reticulate acral and flexural pigmentary disorders are a rare and heterogeneous group of inherited disorders that include Dowling-Degos disease, reticulate acropigmentation of Kitamura, and reticulate acropigmentation of Dohi. Dowling-Degos disease is most commonly caused by keratin 5 (KRT5) mutations and rarely mutations in protein O-glucosyltransferase 1 (POGLUT1) or protein O-fucosyltransferase 1 (POFUT1) genes, while reticulate acropigmentation of Kitamura is caused by ADAM metallopeptidase domain 10 (ADAM10) mutations and acropigmentation of Dohi by mutations in adenosine deaminase, RNA specific (ADAR) gene. Case description: We report a 30-year-old female with a 10-year history of hyperpigmented macules that first appeared on dorsal hands, followed by ventral wrists, dorsal feet, ankles, face, and neck. Family history was positive for similar macules in the patient’s mother, maternal aunt, and maternal grandmother. Results: Physical exam demonstrated hyperpigmented macules on the eyelids, temples, neck, ventral and dorsal wrists, dorsal hands, dorsal feet, lateral and medial ankles, and axillae. Whole exome sequencing from peripheral blood demonstrated a truncating mutation, p.Thr115fs in POFUT1. Additionally, POFUT1 p.Met251Val, a rare variant described in the Single Nucleotide Polymorphism Database (dbSNP), was detected. No definite pathogenic mutations were found in KRT5, POGLUT1, ADAM10, or ADAR genes. Conclusion: This study describes a truncating mutation in POFUT1 gene causing Dowling-Degos disease, one of the reticulate acral and flexural pigmentary disorders.