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Diseases arising from mutations in a single molecule, such as the CFTR in cystic fibrosis exhibit varied clinical phenotypes. The lung cells expressing mutations in CFTR are functioning in the mechanically active environment of the lung, but these mutations may also play an adverse role in the cardiovascular system. Similarly, Marfan syndrome arises from mutations in an extracellular matrix (ECM) molecule, fibrillin\u20101 and this molecule is also involved in tissues operating in very mechanically active environments. Thus, there is the potential for genetic variants with or without clinical symptoms individually to interact in the same individual to exhibit a unique interdependent phenotype involving disruption of the \u201cCell\u2010ECM\u201d relationship. Although the clinical phenotypes for the CFTR and fibrillin\u20101 individually are rare, both molecules are known to each have &gt;500 mutations. This may be one example of a molecular pair that could uniquely interact, influencing cell function. This article will discuss this premise and address the potential basis for complementarity using CFTR and fibrillin\u20101 as examples.<\/jats:p>","DOI":"10.1002\/bies.70138","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T08:52:08Z","timestamp":1776675128000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Could the Phenotypic Outcomes of Genetic Variability in Cells Operating in Mechanically Dynamic Environments be Influenced by a Disrupted \u201cCell\u2010ECM\u201d Relationship? 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