A German team of researchers have found that a gene called SHOX is involved in the development of short stature.
Not only the gene but, the sequences of genetic material on the X and Y chromosome that regulate it are also crucial for growth in children.
Professor Gudrun Rappold, the Director of the Department of Human Molecular Genetics at Heidelberg University Hospital, points out that these gene regulators determine how frequently a gene is copied, and, thus, how effective it is.
In many cases, she says, the mutation of one regulatory sequence of the SHOX gene is sufficient to give rise to the full-blown syndrome.
Publishing their results in the Journal of Medical Genetics, she and her colleagues have said that their findings may open up new possibilities for diagnosing the cause of short stature, and initiating treatment before it is too late.
According to background information in the report, the SHOX gene (short stature homeobox gene) is responsible for the normal growth of bones, and is often mutated in short-stature patients-no more than 160 cm of final height in men, and 150 cm in women.
Hormone disorders, malnutrition, chronic disease, or a genetic disorder are some of the causes of short stature. If, in addition to short stature, other symptoms such as short forearms and lower legs or other bone malformations also occur, it is considered a syndrome.
However, often no exact cause can be determined and other typical features are lacking - this is then known as idiopathic short stature.
In 2007, a research team led by Professor Rappold found that in over 4 percent of children with idiopathic short stature, the trigger for the disorder was a mutation in the SHOX gene. Her latest study has shown that not only the gene itself, but its regulators as well can be crucial for developing the disease.
During the study, the researchers examined the genetic material from a total of 893 subjects.
About 5 percent of the patients with idiopathic short stature, and 80 percent of the patients with Leri-Weill syndrome, had mutations in the segment either including or around the SHOX gene.
The researchers said that some patients had an intact SHOX gene, but an unexpectedly high number of mutations in its enhancer sequences: for 26 percent of patients with SHOX deficiency and idiopathic short stature and for 45 percent of patients with SHOX deficiency and Leri-Weill syndrome, the disease could be attributed solely to a genetic mutation of the enhancer sequence.
"The astounding thing is that this enhancer mutation is quite far away from the affected gene and yet it still leads to the exact same clinical symptoms as a mutation in the gene itself," said Professor Rappold.
The researchers hope that their results will give them a better understanding of the causes of the disease, and allow them to optimize the diagnostic possibilities for patients with SHOX gene mutations.
"Patients who suffer from their short stature often have a great need to be able to name the cause. Even if it is not possible to treat the cause, patients with mutations of the SHOX gene can benefit from a treatment of the symptoms with growth hormones," said Professor Rappold.