Status: Funded - Open
The role of heparin binding growth factors in fetal and childhood growth
Youn Jee, M.D.
BACKGROUND: Both pre- and postnatal growth disorders are common. Approximately 10 % of infants in developed countries have fetal growth restriction and 3% of children are considered to have postnatal growth problems.
GAP: For many newborn, infants and children with growth disorders, either prenatal or postnatal, the etiology remains unknown.
HYPOTHESIS: Two heparin-binding growth factors, midkine (MDK) and pleiotrophin (PTN), are suggested to have a role in body growth in rodents, particularly in early life but their roles in human growth are unknown. We hypothesize that abnormalities in midkine and/or pleiotrophin contribute to fetal and childhood growth disorders.
METHODS: Plasma and urine from healthy children and children with idiopathic growth disorders (Inclusion criteria: age 0-18 y, height SDS < -2, diagnosis of idiopathic short stature including children born small for gestational age and children on growth hormone treatment) and amniotic fluid and maternal plasma from normal pregnancies and pregnancies complicated by IUGR will be studied. Subjects with abnormalities of the MDK/PTN system will be identified and characterized clinically (e.g. malformations, body proportions, inheritance, response to GH treatment), biochemically (e.g. GH-IGF-I axis, thyroid, liver, renal function, markers of malnutrition, malabsorption, and inflammation) and genetically (by copy number microarray and whole exome sequencing, focusing on genes involved in MDK/PTN signaling).
IMPACT: This proposal explores a completely novel area of human growth physiology. It has the potential to provide highly novel and important insights into fetal and childhood growth and to identify new diagnostic and treatment approaches for childhood growth disorders.
National Institutes of Health
Maryland, District of Columbia, Michigan