Systemic causes of CSF rhinorrhea
Jyotirmay S. Hegde, Hemanth Vamanshankar in CSF Rhinorrhea, 2020
Two subtypes have been described:5–7Ehlers-Danlos syndrome classic type: Characterized by joint hypermobility and extensive skin involvement: skin hyperextensibility, abnormal wound healing, and scar formation. Fragility of other connective tissues is also noted, causing cervical insufficiency in pregnancy, recurrent hernias, and rectal prolapse. Cauliflower deformity of skin collagen fibrils on histology is characteristic of the classic type of EDS. Diagnosis is usually clinical, but almost 50% have mutations of the COL5A1 or COL5A2 gene. However, a negative test cannot rule out its absence.Ehlers-Danlos syndrome hypermobility type: This is the more common subtype of EDS. It presents with chronic painful instability of joints associated with joint dislocations. This further leads to degenerative joint disease in young adults. Skin involvement, however, is mild: soft skin that bruises easily. The genetic basis of this subtype is unknown. A positive family history may sometimes be elicited in these patients. Diagnosis is clinical.
Principles of Clinical Diagnosis
Susan Bayliss Mallory, Alanna Bree, Peggy Chern in Illustrated Manual of Pediatric Dermatology, 2005
Major pointsEhlers–Danlos syndrome I. Gravis type (classic, severe): skin fragility and hyperextensibility; soft, velvety skin; joint hypermobility; easily bruised skin; atrophic scars; varicose veins (Figure 20.18)Autosomal dominantBiochemical defect: COL5A1, or COL5A2, or COL1A1Gene locus: 2q31, 17q21.31-q22, 9q34.2-q34.3Ehlers–Danlos syndrome II. Mitis type (classic, mild): similar to type I, but less severe; easily bruised skin; floppy mitral valve; absence of inferior labial frenulum and lingual frenulumAutosomal dominantBiochemical defect: COL5A1, COL5A2Gene locus: 9q34.2-q34.3Ehlers–Danlos syndrome III. Hypermobile type: large and small joint hypermobility (marked) and dislocations; soft skinAutosomal dominantBiochemical defect: COL3A1 and tenascin-XBGene locus: 2q31Ehlers–Danlos syndrome IV. Vascular type: arterial, bowel and uterine rupture; marked skin fragility with thin, translucent skin; easily bruised skin; absence of skin and joint extensibility; tendency to form keloids; characteristic facial
Genetic disorders, skeletal dysplasias and malformations
Ashley W. Blom, David Warwick, Michael R. Whitehouse in Apley and Solomon’s System of Orthopaedics and Trauma, 2017
The inheritance pattern is variable and most cases have an autosomal dominant pattern. There are often abnormalities of collagen formation, commonly involving mutations of COL5A1 or COL5A2 with COL1A1, COL1A2 and COL3A1 also reported.
Management of progressive pulmonary fibrosis associated with connective tissue disease
Published in Expert Review of Respiratory Medicine, 2022
María Molina-Molina, Iván Castellví, Claudia Valenzuela, José Ramirez, José Antonio Rodríguez Portal, Tomás Franquet, Javier Narváez
The pathogenesis of ILD associated with CTD (CTD-ILD) is not completely elucidated, although the main hypothesis assumes that tissue fibrosis is preceded by an immune-mediate process [1–6,13–16]. In SSc, this process seems to be triggered by endothelial injury in the context of encompassing immune activity [3,14,15]. In the last decades, some research studies have suggested different pathways to be implicated in the development of ILD in SSc and RA, including immune-mediated alveolar epithelial damage and endothelial disorders, and the subsequent and progressive abnormal extracellular matrix remodeling and myofibroblast formation [17]. Following the identification of these pathogenic pathways and implicated mediators, different future potential strategies are being pre-clinically evaluated in SSc-associated ILD (SSc-ILD) and RA-associated ILD (RA-ILD), including the regulation of some relevant overexpressed extracellular matrix proteins such as COL5A2 [18,19].
Long noncoding RNA/circular RNA regulates competitive endogenous RNA networks in rheumatoid arthritis: molecular mechanisms and traditional Chinese medicine therapeutic significances
Published in Annals of Medicine, 2023
Jianting Wen, Jian Liu, Lei Wan, Fanfan Wang
Certain ceRNA networks are linked to the viability and apoptosis of RA. Wang et al. in their work suggested that the LINC00152/miR-1270/FOXM1 axis influences the pathogenesis of RA [47]. Depletion of lncRNA ZFAS leads to an inhibition in viability and an enhancement in apoptosis of RA-FLSs via the miR-2682-5p/ADAMTS9 axis [48]. Zheng et al. also stated that lncRNA RNA ZFAS1 results in the suppression of the RA process through the miR-296-5/MMP-15 axis [97]. Downregulation of lncRNA GAS5 results in suppressed proliferation and induced apoptosis via the modulation of the miR-361-5p/PDK4 axis [62]. CircFADS2 and mTOR were upregulated but miR-498 was downregulated in TNF-α-induced RA-FLS. Moreover, CircFADS2 could mediate mTOR expression via binding to miR-498, and CircFADS2 stimulated mitophagy via the miR-498/mTOR axis [71]. Furthermore, lncRNA OIP5-AS1/miR-448/TLR3/NF-κB, lncRNA BZRAP1-AS1/miR-1286/COL5A2 and LncRNA XIST/miR-126-3p/NF-κB have been found to strengthen proliferation and restrict apoptosis of RA-FLS [49,54,58].
Altered long non-coding RNAs expression in normal and diseased primary human airway epithelial cells exposed to diesel exhaust particles
Published in Inhalation Toxicology, 2023
C. M. Sabbir Ahmed, Alexa Canchola, Biplab Paul, Md Rubaiat Nurul Alam, Ying-Hsuan Lin
On the other hand, lncRNA SNHG29 (also named as LRRC75A-AS1) that activates the p53/p21 signaling and results in cell senescence (Jiang et al. 2021) was found downregulated in DHBE-COPD cells (log2FC = −6.42, FDR value = 1.82E-05), while its trans-targeted gene COL5A2 (Collagen Type V Alpha 2 Chain) was found to be upregulated (Figure 6). Recent studies reported that the gene expression of COL5A2 was significantly upregulated in colorectal cancer (Wang et al. 2021b), gastric cancer (Tan et al. 2021), bladder cancer (Zeng et al. 2018), and prostate cancer (Ren et al. 2021). The expression pattern indicates the potential risk of DHBE-COPD cells in cancer development (Figure 6).
Related Knowledge Centers
- Protein
- Type V Collagen
- Gene
- Ehlers–Danlos Syndromes