Date of Award
Medical Doctor (MD)
Dupuytren's disease is a common heritable connective tissue disorder of poorly understood etiology. It is thought that oxidative stress pathways may play a critical role in the development of Dupuytren's disease, given the various disease associations that have been observed. We sought to sequence the mitochondrial and nuclear genomes of patients affected with Dupuytren's disease using next-generation sequencing technology to potentially identify genes of potential pathogenetic interest. Additionally, we sought to compare the genomes between diseased tissue and blood to look for potential somatic mutations in the diseased tissue. Upon sequencing and subsequent bioinformatics analysis, no differences were observed in the mitochondrial and nuclear genomes between diseased tissue and blood. However, when we compared the nuclear genome of our patient cohort to a control cohort, we observed some significant genetic differences. We identified a number of single nucleotide polymorphisms (SNPs) and mutations that are potentially associated with Dupuytren's disease. Additionally, 2 novel mutations leading to amino acid changes were present in all patients in the disease cohort but not in the controls. These were mutations in MUC4, encoding mucin 4, and PPP1R32, encoding protein phosphatase 1 regulatory subunit 32. These genes warrant further investigation in the pathophysiology of Dupuytren's disease.
Sue, Gloria, "The Genetic Basis Of Dupuytren's Disease" (2014). Yale Medicine Thesis Digital Library. 1926.