Akademik Veri Yönetim Sistemi
33rd EADV Congress, Amsterdam, Hollanda, 25 - 28 Eylül 2024, cilt.17, ss.144-145, (Özet Bildiri)
Introduction & Objectives: Dowling-Degos disease (DDD) is a rare automosomal dominant genodermatosis characterized by the gradual emergence of reticulated pigmented lesions, primarily affecting flexural regions of the skin. The pathogenesis is linked to mutations in specific genes, including POFUT1. Materials & Methods: Here we report a patient with flexural hyperpigmentation who was diagnosed as DDD with novel pathogenic variant of the POFUT1 gene based on clinical, histopathological and genetic findings. Results: A 51-year-old Turkish female patient presented with asymptomatic, bilateral pigmented axillary and inguinal lesions that had developed over 10 years. Dermatological examination revealed reticular hyperpigmented macules and patchs on her face, neck, bilateral axillae, arms, hand dorsums, inframammarian folds, intermammarian area and inguinal areas and pits on bilateral palmar regions. Histopathological analysis of hiperpigmented patch from intermammary area showed regular epidermal hyperplasia, keratin cysts in the epidermis, elongation of the rete ridges, focal pigment increase in the tips of rete. Genomic DNA was extracted from the patient’s peripheral blood sample. Whole exome DNA sequencing identified a novel heterozygous mutation, NM_015352.2:c.1047dupC NP_056167.1 (p.Phe350LeufsTer34) in POFUT1. The patient was diagnosed with DDD. She was initiated on oral isotretinoin treatment, but discontinued the drug due to its adverse effects. Conclusion: DDD is a benign genodermatosis classified as a reticular pigmented dermatosis. The lesions typically manifest in adulthood between the second and fifth decade on flexural sites, presenting as symmetric and progressive macular reticular hyperpigmentation with reddish-brown papules and plaques. DDD is associated with mutations in the keratin 5, POGLUT1, POFUT1 and PSENEN genes. In 2013, Li et al. identified a POFUT1 gene mutation on chromosome 20q11. The POFUT1 gene encodes the protein Ofucosyltransferase 1, which is related to NOTCH receptors. The results of the functional analysis demonstrated that POFUT1 plays a role in melanin synthesis and transport. The genetic analysis revealed the presence of a novel pathogenic heterozygous variant, NM_015352.2(POFUT1):c.1047dupC (p.Phe350LeufsTer34), in our patient. This variant has not been previously reported in the databases of the National Center for Biotechnology Information (NCBI), the Database of Single Nucleotide Polymorphisms (dbSNP), the Human Gene Mutation Database (HGMD® Professional 2023.3), or the Clinical Variation Database (ClinVar). In the literature, a range of clinical findings have been reported in DDD patients associated with different POFUT1 gene mutations. In accordance with the majority of previous reports, the intertriginous regions, face, arms and hand dorsums were affected in our patient. Furthermore, the presence of palmar pits, which has been reported in a few cases, was also present. A few cases of DDD have been reported in the literature with distinct clinical findings, including an association with HS and multiple seborrheic keratoses. However, our patient did not demonstrate these associations. This novel mutation, c.1047dupC (p.Phe350LeufsTer34), is reported herewith to contribute to the POFUT1 gene database. Further reports may be helpful in elucidating the relationship between pathogenic variations of the POFUT1 gene and different phenotypes.