One of the major causes of short stature is a mutated SHOX gene. Understanding how mutations of the gene and its regulatory regions cause restricted growth could lead to improved methods of diagnosing short stature and new treatments.
What Affects Short Stature?
Short stature is typically considered when 160cm is the final growth height for men, and 150cm is the final growth height for women. There are many factors that affect short stature including malnutrition, chronic hormone deficiencies, rickets, Cushing's disease, and delayed puberty. Short stature also results from genetic mutations.
The SHOX gene (short stature homeobox gene) is responsible for normal bone growth, but in 2007 Professor Gudrun Rappold, (Director of the Department of Human Molecular Genetics at Heidelberg University Hospital) discovered that this gene was mutated in 4% of children with idiopathic short stature.
One copy of each gene is located on each sex chromosome (X and Y) and it is responsible for the growth of epiphyseal plates which are found in growing bones. SHOX codes for a protein that is a transcription factor involved in the growth and maturation of bones in the arms and legs. However, mutations of the SHOX gene lead to people growing to a height of 20cm less than expected. And the problem does not just lie with the mutated gene; mutations in regulatory regions of this gene can also bring about short stature. This was discovered by Professor Rappold's team in 2009.
The researchers at Heidelberg University Hospital examined 893 people with short stature and found that 5% of those with idiopathic short stature, and 80% of those with Leri-Weill Syndrome (a rare form of dwarfism) had mutations either in the SHOX gene or in the regions around it. Some people with intact SHOX genes had high levels of mutations solely in the enhancer sequences and still presented with the same clinical symptoms.
Therefore the researchers have shown that these regulatory regions as well as the genes are important in regulating the growth of children. By understanding more about the molecular basis of short stature scientists hope that it will help them develop better diagnostic tools to be able to spot the condition earlier, and to then tailor appropriate treatments of the symptoms with growth hormones. They may even discover molecular pathways that could provide new targets for therapeutics. The scientists also state that many people with short stature want to know the exact cause of it, and research like this helps them to understand more about why their growth arrested.