An American Board of Medical Genetics-certified clinical biochemical geneticist and medical geneticist, Dr. Hart uses molecular and biochemical techniques to understand genetic diseases of the teeth, the oral cavity, and the kidney.
Gingival tissue plays an important role in tooth development, with gum health contributing to overall well-being, appearance, and the ability to eat and speak properly. Overgrowth of the gums can occur as an isolated inherited condition, as part of a genetic syndrome, or as a side effect of certain medications. In 2002, Dr. Hart and colleagues discovered the only gene mutation known to be involved in hereditary gingival fibromatosis (HGF), a rare autosomal dominant form of gum overgrowth. The mutated gene, SOS1, normally encodes a protein that activates the ras pathway, a key growth signaling pathway in cells. The Hart laboratory is also studying syndromic forms of gingival overgrowth, such as Zimmerman-Laband syndrome and juvenile hyaline fibromatosis, as well as gingival overgrowth attributed to various medications.
In a related area of study, Dr. Hart investigates the molecular causes of disorders that affect the enamel or dentin inside teeth. Of particular interest to her research are isolated tooth defects, as well as syndromes where tooth anomalies occur. The genes expressed in the developing tooth are difficult to analyze; teeth are mineralized structures. Therefore, the isolation of RNA needed to study gene expression in teeth is difficult. Her group conducts mutation analysis and uses linkage-type approaches to study genes involved in normal tooth development, and has discovered mutations in a number of these (e.g., AMELX, ENAM, KLK4, MMP20, and DSPP). A large collection of samples compiled by Dr. Hart's group since 1991 forms the foundation for this research. These samples are routinely re-examined as new genomic technologies become available, enabling the identification of additional genes involved in the development of tooth defects.
Dr. Hart collaborated with the research group that identified the CTCS gene, which was found to be mutated in Papillon-Lefevre syndrome. This autosomal recessive disorder is characterized by keratosis of the palms and soles of the feet, as well as pronounced periodontal disease. Children with this condition suffer mouth inflammation and problems with their newly erupted teeth. Primary teeth are typically lost by age 4, with further exfoliation and loss of permanent teeth by age 20.
Dr. Hart also conducts research on medullary cystic kidney disease (MCKD), an inherited disorder associated with gradual loss of kidney function. In 2002, Dr. Hart and colleagues identified UMOD on chromosome 16 as the causative gene in MCKD type 2, a hereditary endoplasmic reticulum storage disease associated with kidney failure. They have also identified REN mutations as the cause of one form of anemia and chronic kidney failure. Currently, her laboratory is actively trying to identify the causative gene for MCKD type 1, a disorder in which patients have normal kidney function through childhood but later develop renal failure and ultimately require kidney transplantation. The identification of the underlying genetic causes of various forms of kidney disease may lead to new therapeutic approaches.
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Last Updated: May 18, 2014