International Team Identifies Defect Among a 23,000-member Brazilian Family
A search for the genetic roots of towering height has led a Johns Hopkins endocrinologist to identify a mutation that causes a rare form of treatable dwarfism. Research results, published in the March issue of the Journal of Clinical Endocrinology and Metabolism, suggest that the mutation could be used as a prenatal screening test for the disorder.
After speaking at a meeting in Washington in 1996, Michael A. Levine, M.D., an authority on acromegaly -- a growth hormone disorder characterized by large hands and feet -- was invited by Brazilian researchers to consult on several families of giants seen at the University of S o Paulo Hospital clinic. There, Levine noticed two patients in the waiting area who were unusually small. While he continued to look for the genetic basis for the tall patients, he asked permission to start another study of the shorter ones.
By analyzing DNA samples, Levine, endocrinology instructor Roberto Salvatori, M.D., and an international team of collaborators went on to pinpoint the mutation responsible for dwarfism among at least 105 members of an extended family of Portuguese descent in Sergipe, a remote area in northeastern Brazil. The family comprises 23,000 individuals.
All of the affected family members, whose average height is three and a half feet, inherited defective genes that knock out the receptor for growth hormone releasing hormone (GHRHR). The tiny change in the genetic code for the receptor makes it impossible for chemical signals that stimulate growth of bones to be "heard"; therefore, bone growth is markedly impaired.
The study suggests that defects in the receptor may be a more common cause of growth hormone deficiency than previously suspected, Levine says.