Genetics of Birth Defects: neuroendocrine, auditory, and skeletal development. Pituitary hormone deficiency diseases and adenomas are both common in humans. Many combined hormone deficiencies are caused by transcription factor defects. Lesions in the homeodomain transcriprion factor gene PROP1 are most prevalent cause of multiple pituitary hormone deficiencies, and defects in PITX2 cause Rieger syndrome, which can include growth hormone deficiency. We study Prop1, Pitx2, and other pituitary transcription factor genes using genetically engineered mice. About half the cases of congenital deafness are thought to be genetic. We are studying the function of the motor myosin gene Myo15 in sensory hair cell development and function.
Environmental factors such as thyroid hormone deficiency can cause profound deafness if untreated, although genomic effects influence the susceptibility to hypothyroidism induced hearing impairment. We are identifying genes that protect against this form of deafness. Skeletal dysplasias are a highly heterogeneous group of birth defects, and the etiology is unknown for many cases. We are pursuing the genetics, pathophysiology and therapy for skeletal dysplasia in mouse models.