{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nDNA copy number variations (CNVs) have been implicated in the pathogenesis of diverse human disorders, including congenital birth defects such as oral clefts. Studies have demonstrated that both small and large chromosomal deletions contribute to multisystem defects in individual patients."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent research into inherited CNVs in cancer has revealed that the ADAM5 pseudogene plays a role in modulating oropharyngeal squamous cell carcinoma (OPSCC) risk. Specifically, individuals with three or more copies of the ADAM5 (along with ADAM3A) pseudogene at the 8p11.22 region exhibit an approximately 6.5‐fold increased risk of developing OPSCC. Notably, ADAM5 contains a sequence highly homologous to the 3′-untranslated region (3′-UTR) of ADAM9, which is predicted to serve as a binding site for miR-122b-5p. This suggests that the ADAM5 pseudogene transcript may act as a competitive binding sink for miR-122b-5p, leading to a deregulated increase in ADAM9 expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn summary, ADAM5 appears to function as a regulatory pseudogene with potential implications in both altered developmental pathways and cancer. By influencing miR-122b-5p availability and thereby modulating ADAM9 expression, changes in ADAM5 copy number may contribute not only to cancer susceptibility but also to worse prognostic outcomes in OPSCC patients. These findings underscore the broader importance of CNVs and pseudogene-mediated regulatory mechanisms in human disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Samuel G Younkin, Robert B Scharpf, Holger Schwender, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genome-wide study of inherited deletions identified two regions associated with nonsyndromic isolated oral clefts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Birth Defects Res A Clin Mol Teratol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/bdra.23362"}], "href": "https://doi.org/10.1002/bdra.23362"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25776870"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25776870"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Juliana Carron, Caroline Torricelli, Janet Keller Silva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of Inherited Copy Number Variation in "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "ADAM3A"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " and "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "ADAM5"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Pseudogenes with Oropharynx Cancer Risk and Outcome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes (Basel) (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/genes13122408"}], "href": "https://doi.org/10.3390/genes13122408"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36553675"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36553675"}]}]}]}