Idiopathic short stature (Idiopathic short stature - ISS) - Gene SHOX
About 3% of the population is short and most of them are unaware of the causes. Growth is a multifactorial trait that results from a complex interplay between several genes and multiple environmental factors. However, a significant percentage of growth failures result from alteration of a gene designated SHOX (Short stature homeobox-container containing gene).
This gene is part of (pseudoautosomal Region gene family: gene family pseudoautosomal region) PAR genes, which are located near the ends of the sex chromosomes X and Y. In these regions PAR, there are genes found on both chromosomes X and Y, so both man and woman, have two functional copies in each cell. The seudoautosómicas regions of the X and Y chromosomes PAR1 and PAR2 are known, being the PAR1 region at the end of the short arm of chromosomes and contains 27 both genes. PAR2 is the region on the long arm of both chromosomes. In males, the seudoautosómicas regions are needed to properly align the X and Y chromosomes during cell division. Mating pair 1 XY seems essential for the normal formation of spermatogenesis and a loss of PAR1 be related to male infertility. The PAR2 region does not seem necessary for fertility.
Many genes of PAR1 and PAR2 are important for development, but only the SHOX gene region PAR1 has been linked to two genetic abnormalities: Leri-Weill discondrostosis, and Langer mesomelic dysplasia. Turner's syndrome is missing one copy of SHOX gene in women, and have stature and skeletal abnormalities. Moreover, some variations SHOX have been associated with short stature in people with no other signs (idiopathic short stature).
The SHOX gene is located on the short arm of chromosome X and Y (Xp22.33; Yp11.3) pseudoautosomal region PAR1 in. The protein encoded by this gene is a transcription factor that plays a role in bone development and is particularly important for the growth and maturation of bones in the arms and legs. A copy of SHOX gene is on each of the sex chromosomes in an area called the pseudoautosomal region. Genes in the pseudoautosomal region are present on both chromosomes. As a result, women (who have two X chromosomes) and men (having an X and a Y chromosome) have two functional copies of the gene in every cell SHOX. It has also been shown that there is a direct association between the number of active copies SHOX and height.
Deletions of all or SHOX mutations in or near the gene have been identified in some individuals with short stature. This short height is generally described as idiopathic, meaning that is not associated with the characteristics of a disease or syndrome. However, there have been reports of individuals with short stature and changes in the SHOX gene having minor skeletal abnormalities. Mutations in the gene SHOX occurring heterozygous plus associated with idiopathic short stature, are associated with Leri-Weill discondrostosis and Turner syndrome. Homozygous are associated with the most severe form, called mesomelic Dysplasia Langer. Most mutations detected in the SHOX gene are deletions (70%), so it is recommended to start the study by MLPA analysis (Multiple Ligation-Dependent Probe--Assay), or their equivalents. In its coding sequence they have been identified so far, more than 60 different mutations.
Tests in IVAMI: in IVAMI perform detection of mutations associated with idiopathic short stature, by complete PCR amplification of exons SHOX and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).