The Endocrinology Research Laboratory has focused on genetic causes of short stature in children. Over the last 20 years we have identified several gene abnormalities (mutations) that cause growth failure and heights below the first percentile.
Genetic and environmental conditions can interfere with normal growth in childhood. In some children, the growth problems are caused by changes in certain genes within the body’s cells. Genes are made of DNA, the substance in the cell that stores genetic information, and are responsible for passing particular traits such as eye color from parents to children. Genes direct cells in the body to make proteins, many of which are required for growth. In some instances of severe short stature, mutations in certain genes cause cells to produce abnormal proteins. In some cases the affected gene no longer makes the growth hormone required for growth. In other cases, the abnormal proteins prevent normal development of the pituitary gland so that the abnormal pituitary is unable to produce several hormones that are required for normal growth, thyroid gland function and in some cases, puberty.
Our previous work identified mutations in the growth hormone gene that cause isolated growth hormone deficiency. We characterized mutations in the growth hormone receptor gene that cause growth hormone insensitivity syndrome. More recently, we identified mutations in the POU1F1 and PROP1 genes that interfere with pituitary development and lead to multiple pituitary hormone deficiencies.
Our current research interests include both normal and disease-related variations in genes that affect growth and height in children. We are continuing our study of the PROP1 gene by defining the patterns of inheritance of specific gene mutations that cause multiple pituitary hormone deficiency and severe short stature. The study of PROP1 mutations may reveal how the protein interacts with other growth factors and controls the growth of cells in the fetal pituitary gland. The findings will help identify population groups that are more likely to carry abnormal PROP1 genes.
Our primary research project concerns the contribution of normal gene variations to idiopathic short stature (short stature with no apparent cause). We are examining normal variations in several growth-related genes. These variations do not directly cause a disease but acting alone or in combination may change susceptibility to growth problems. Identification of the different types of genetic variation that contribute to idiopathic short stature may lead to improved understanding of the causes of short stature, improved methods of diagnosis, and to tailoring treatment to the specific causes of growth failure.
In addition to studies of short stature, we are currently participating in a collaborative study with Erasmus Medical Center in the Netherlands to identify gene variations associated with extreme tall stature in healthy adults. This study will further our understanding of the genetic control of height.