Genetic and Phenotypic Features of 2 Northern Italy Families with Dowling-Degos Disease Type 4
Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis involving the folds with lentiginous hyperpigmentation and reddish–brown papules. Four main types of DDD with variable clinical presentations likely related to the heterogeneity of the gene variant landscape have been implicated. Pa...
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Elsevier
2025-07-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667026725000207 |
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| author | Dario Tomasini Carlo F. Tomasini Andrea Michelerio Eloisa Arbustini Fabio Sirchia Alrun Hotz Judith Fischer Svenja Rademacher |
| author_facet | Dario Tomasini Carlo F. Tomasini Andrea Michelerio Eloisa Arbustini Fabio Sirchia Alrun Hotz Judith Fischer Svenja Rademacher |
| author_sort | Dario Tomasini |
| collection | DOAJ |
| description | Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis involving the folds with lentiginous hyperpigmentation and reddish–brown papules. Four main types of DDD with variable clinical presentations likely related to the heterogeneity of the gene variant landscape have been implicated. Pathogenic keratin 5 gene K5 gene variants favor a reticular distribution with predominant fold involvement, whereas pathogenic variants in POGLUT1 lead to a widespread form with acantholytic features previously named Galli–Galli disease, now belonging to the disease spectrum of DDD and renamed DDD type 4. This study details the clinical and histopathological features associated with the sequence variant c.205C>T, p.(Arg69∗) in POGLUT1 of 2 families from northern Italy affected by DDD4. Despite sharing the same variant, clinical manifestations varied among the affected members of the 2 families. Environmental factors probably contributed to phenotypic variability and symptoms exacerbation. Histopathology was sustained by digitiform rete ridges, suprabasal acantholysis, and dyskeratosis. Moreover, we detected aberrant keratin 5 gene K5 expression in 2 biopsies. A review of the literature on POGLUT1-related DDD subtypes contextualizes these findings. The fact that several patients have been reported to carry the variant c.205C>T, p.(Arg69∗) might point to a potential mutational hotspot. |
| format | Article |
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| institution | OA Journals |
| issn | 2667-0267 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
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| spelling | doaj-art-00abea9fa7264152b38d9b62549a8e6d2025-08-20T02:36:49ZengElsevierJID Innovations2667-02672025-07-015410036410.1016/j.xjidi.2025.100364Genetic and Phenotypic Features of 2 Northern Italy Families with Dowling-Degos Disease Type 4Dario Tomasini0Carlo F. Tomasini1Andrea Michelerio2Eloisa Arbustini3Fabio Sirchia4Alrun Hotz5Judith Fischer6Svenja Rademacher7Division of Dermatology, Medical Department, ASST Valle Olona, Hospital of Busto Arsizio, Busto Arsizio, Italy; Correspondence: Dario Tomasini, Division of Dermatology, Medical Department, ASST Valle Olona, Hospital of Busto Arsizio, Busto Arsizio, Italy.Department of Clinical-Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, ItalyDermatology Clinic, IRCCS San Matteo Foundation, Pavia, ItalyTransplant Research Area and Centre for Inherited Cardiovascular Diseases, Department of Medical Sciences and Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, ItalyDepartment of Molecular Medicine, University of Pavia, Pavia, Italy; Medical Genetics Unit, IRCCS San Matteo Foundation, Pavia, ItalyInstitute of Human Genetics, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, GermanyInstitute of Human Genetics, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, GermanyInstitute of Human Genetics, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDowling-Degos disease (DDD) is an autosomal dominant genodermatosis involving the folds with lentiginous hyperpigmentation and reddish–brown papules. Four main types of DDD with variable clinical presentations likely related to the heterogeneity of the gene variant landscape have been implicated. Pathogenic keratin 5 gene K5 gene variants favor a reticular distribution with predominant fold involvement, whereas pathogenic variants in POGLUT1 lead to a widespread form with acantholytic features previously named Galli–Galli disease, now belonging to the disease spectrum of DDD and renamed DDD type 4. This study details the clinical and histopathological features associated with the sequence variant c.205C>T, p.(Arg69∗) in POGLUT1 of 2 families from northern Italy affected by DDD4. Despite sharing the same variant, clinical manifestations varied among the affected members of the 2 families. Environmental factors probably contributed to phenotypic variability and symptoms exacerbation. Histopathology was sustained by digitiform rete ridges, suprabasal acantholysis, and dyskeratosis. Moreover, we detected aberrant keratin 5 gene K5 expression in 2 biopsies. A review of the literature on POGLUT1-related DDD subtypes contextualizes these findings. The fact that several patients have been reported to carry the variant c.205C>T, p.(Arg69∗) might point to a potential mutational hotspot.http://www.sciencedirect.com/science/article/pii/S2667026725000207Clinical researchCytoskeletonGenetic diseasesGenodermatosisHuman genetic |
| spellingShingle | Dario Tomasini Carlo F. Tomasini Andrea Michelerio Eloisa Arbustini Fabio Sirchia Alrun Hotz Judith Fischer Svenja Rademacher Genetic and Phenotypic Features of 2 Northern Italy Families with Dowling-Degos Disease Type 4 JID Innovations Clinical research Cytoskeleton Genetic diseases Genodermatosis Human genetic |
| title | Genetic and Phenotypic Features of 2 Northern Italy Families with Dowling-Degos Disease Type 4 |
| title_full | Genetic and Phenotypic Features of 2 Northern Italy Families with Dowling-Degos Disease Type 4 |
| title_fullStr | Genetic and Phenotypic Features of 2 Northern Italy Families with Dowling-Degos Disease Type 4 |
| title_full_unstemmed | Genetic and Phenotypic Features of 2 Northern Italy Families with Dowling-Degos Disease Type 4 |
| title_short | Genetic and Phenotypic Features of 2 Northern Italy Families with Dowling-Degos Disease Type 4 |
| title_sort | genetic and phenotypic features of 2 northern italy families with dowling degos disease type 4 |
| topic | Clinical research Cytoskeleton Genetic diseases Genodermatosis Human genetic |
| url | http://www.sciencedirect.com/science/article/pii/S2667026725000207 |
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