Molecular Carcinogenesis Program, Brazilian National Cancer Institute (INCA), Rio de Janeiro, Brazil.
Department of Dermatology, Federal Hospital of Bonsucesso, Rio de Janeiro, Brazil.
Am J Med Genet A. 2020 Nov;182(11):2662-2665. doi: 10.1002/ajmg.a.61800. Epub 2020 Aug 17.
Dowling-Degos disease (DDD) is a rare autosomal-dominant genodermatosis and it has been associated with hidradenitis suppurativa (HS). Deregulation of NOTCH pathway has been linked to the development of HS in DDD context (DDD-HS). However, molecular alterations in DDD-HS, including altered gene expression of NOTCH and downstream effectors that are involved in the follicular differentiation and inflammatory response, are poorly defined. We report two cases of patients diagnosed with DDD-HS, one of those, under Adalimumab treatment. Our results have shown downregulation of NOTCH1/NCSTN pathway, distinct molecular profiles of inflammatory cytokines (IL23A and TNF), and a novel aberrant upregulation of genes involved in the cornified envelope (CE) formation (SPRR1B, SPRR2D, SPRR3, and IVL) in paired HS lesions of two DDD patients.
Dowling-Degos 病（DDD）是一种罕见的常染色体显性遗传皮肤病，与化脓性汗腺炎（HS）有关。NOTCH 通路的失调与 DDD 背景下 HS 的发展有关（DDD-HS）。然而，DDD-HS 中的分子改变，包括参与滤泡分化和炎症反应的 NOTCH 和下游效应物的基因表达改变，定义不明确。我们报告了两例诊断为 DDD-HS 的患者，其中一例接受阿达木单抗治疗。我们的结果表明，NOTCH1/NCSTN 通路下调，炎症细胞因子（IL23A 和 TNF）的分子谱不同，以及涉及角蛋白包膜（CE）形成的基因的新型异常上调（SPRR1B、SPRR2D、SPRR3 和 IVL）在两名 DDD 患者的配对 HS 病变中。
