Forward Genetic Analysis of Congenital Craniofacial Malformations
PrincipaI Investigator: Rolf Stottmann, PhD
Key Personnel: Patricia Bender, RN, MSN, Samantha Brugmann, PhD, Chris Gordon, MD, Robert Hopkin, MD, Rulang Jiang, PhD, Yu Lan, PhD, Cynthia Prows, MSN, APRN, CNS, Howard Saal, MD, FACMG, Kristen Sund, PhD, LGC, Kathryn Nicole Weaver, MD, John van Aalst, MD
Craniofacial anomalies are conditions where the face does not form into the appropriate shapes at birth. Craniofacial anomalies are among the most common congenital birth defects affecting greater than 1 in 700 live births. Although craniofacial anomalies have a large genetic component, we lack a full understanding of the gene networks and mechanisms involved. This study is designed to identify the genetic causes of congenital craniofacial malformations associated with rare of unique syndromes seen in Cincinnati Children's clinics. We will utilize whole exome sequencing to identify the causal genes in these rare disorders. We will use recently developed genetic tools to sequence the DNA of affected individuals and their family members. In this way, we can identify which change(s) in the DNA sequence caused the craniofacial birth defect. We then proceed to study in the laboratory why that change in DNA leads to the birth defect. We do this with a combination of experiments, including the production of animal models of the human mutations. These findings offer new understanding of birth defects, possibly extending well beyond craniofacial biology, which could be developed as genetic tests or as the basis for novel therapeutic strategies.