ABSTRACT
Birt-Hogg-Dubé syndrome is a genodermatosis of autosomal dominant inheritance characterized by mutations in the folliculin (FLCN) gene. There is an inappropriate inhibition/activation of a protein, the foliculin, which may cause tumor lesions in skin, renal and lung lesions; they could have more risk of developing pneumothorax compared to the normal population. A 38-year-old male patient with bronchial asthma who consulted for hemoptysis three weeks after recovery from COVID-19 infection. A chest tomography was requested, showing an air cyst in the left lower lobe. Physical examination shows evidence of thoracic skin lesions which a skin biopsy was performed on. The results were compatible with fibrofolliculoma. Differential diagnoses were proposed. A genetic disorder associated with skin lesions was suspected. A multi-genetic panel that includes BRCA1, BRCA2, TP53 and FLCN genes was requested, which reported the mutation of the FLCN gene in heterozygosis classified as pathognomonic of Birt-Hogg-Dubé syndrome. Patient is currently under clinical follow-up while genetic counseling was requested for relatives.
El síndrome de Birt-Hogg-Dubé es una genodermatosis de herencia autosómica dominante caracterizada por mutaciones en el gen foliculina (FLCN), donde existe inhibición/activación inapropiada de una proteína, la foliculina, que puede causar lesiones tumorales sistémicas, principalmente a nivel de la piel, renal y lesiones pulmonares, presentando mayor riesgo de desarrollar neumotórax en comparación con la población normal. Comunicamos el caso de un varón de 38 años con asma bronquial que consultó por hemoptisis 3 semanas después de la recuperación de la infección por COVID-19. Se solicitó una tomografía de tórax, que mostró un quiste aéreo en el lóbulo inferior izquierdo. Además, presentaba en el examen físico una lesión cutánea que fue biopsiada, presentando diagnóstico de foliculoma. Se plantearon diagnósticos diferenciales y ante la sospecha de probable desorden genético, un panel genético fue solicitado. Se confirmó síndrome de Birt-Hogg-Dubé ante el hallazgo de la deleción heterocigota que comprende el exón 1 del gen FLCN clasificada como patogénica. Actualmente el paciente se encuentra en seguimiento clínico mientras se solicitó estudio genético para familiares.
Subject(s)
Birt-Hogg-Dube Syndrome , COVID-19 , Pneumothorax , Male , Humans , Adult , Birt-Hogg-Dube Syndrome/diagnosis , Birt-Hogg-Dube Syndrome/genetics , Birt-Hogg-Dube Syndrome/pathology , Hemoptysis , Tumor Suppressor Proteins/genetics , Pneumothorax/geneticsABSTRACT
Acute lung injury (ALI) is characterized by acute systemic inflammatory responses that may lead to severe acute respiratory distress syndrome (ARDS). The clinical course of ALI/ARDS is variable; however, it has been reported that lipopolysaccharides (LPS) play a role in its development. The fragile chromosomal site gene WWOX is highly sensitive to genotoxic stress induced by environmental exposure and is an important candidate gene for exposure-related lung disease research. However, the expression of WWOX and its role in LPS-induced ALI still remain unidentified. This study investigated the expression of WWOX in mouse lung and epithelial cells and explored the role of WWOX in LPS-induced ALI model in vitro and in vivo. In addition, we explored one of the possible mechanisms by which WWOX alleviates ALI from the perspective of autophagy. Here, we observed that LPS stimulation reduced the expression of WWOX and the autophagy marker microtubule-associated protein 1 light chain 3ß-II (MAP1LC3B/LC3B) in mouse lung epithelial and human epithelial (H292) cells. Overexpression of WWOX led to the activation of autophagy and inhibited inflammatory responses in LPS-induced ALI cells and mouse model. More importantly, we found that WWOX interacts with mechanistic target of rapamycin [serine/threonine kinase] (mTOR) and regulates mTOR and ULK-1 signaling-mediated autophagy. Thus, reduced WWOX levels were associated with LPS-induced ALI. WWOX can activate autophagy in lung epithelial cells and protect against LPS-induced ALI, which is partly related to the mTOR-ULK1 signaling pathway.