Leri-Weill dyschondrosteosis (Leri-Weill dyschondrosteosis) - Gene SHOX
The Leri-Weill dyschondrosteosis or Leri-Weill syndrome of, is a skeletal dysplasia characterized by short stature, mesomelia and Madelung deformity wrist. Generally , the phenotype is stronger in women than in men, perhaps due to the different levels of estrogen between the sexes.
Most cases of Leri-Weill dyschondrosteosis are due to changes in the SHOX, located on the short arm of the X chromosome and the short arm of chromosome Y (Xp22.33; Yp11.3). 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, whose genes are located on both chromosomes. As a result, women who have two X chromosomes, and men, who have an X and a Y chromosome having two functional copies of the gene in every cell SHOX.
The most common cause of Leri-Weill dyschondrosteosis is a deletion of the entire gene SHOX. Other genetic changes responsible for the disease include mutations in the SHOX or deletions of genetic material nearby normally help regulate gene activity. These changes reduce the amount of protein encoded SHOX. A deficiency of this protein alters the normal development and bone growth, which underlies the main characteristics of Leri-Weill dyschondrosteosis. In those affected who have a genetic change that involves the SHOX gene, the cause of the disease is unknown.
Mutations in the gene SHOX occurring heterozygous, besides Leri-Weill dyschondrosteosis are associated with mild forms of idiopathic short stature and Madelung deformity isolated - see -gen SHOX- idiopathic short stature. Homozygous, associated with the most severe form, mesomelic Dysplasia Langer - see Langer mesomelic dysplasia - SHOX- gene.
The Leri-Weill dyschondrosteosis has a pattern pseudoautosomal dominant inheritance. The SHOX gene is both chromosomes X and Y, in an area known as the pseudoautosomal region. Although many genes are unique to either the X or Y chromosome, genes in the region pseudoautosomal are present in both sex chromosomes. As a result, both women who have two X chromosomes, such as men who have an X and a Y chromosome, usually have two functional copies of the gene in every cell SHOX. The inheritance pattern of Leri-Weill dyschondrosteosis described as dominant because an absent or altered SHOX copy in each cell is sufficient to express the disease. In women, the disease is expressed when the gene is absent or altered in one of the two copies of the X chromosome; in males, the disease is expressed when the gene is absent or altered in either the X or the Y chromosome
Tests performed in IVAMI: in IVAMI perform detection of mutations associated with Leri-Weill dyschondrosteosis by the complete PCR amplification of exons SHOX and subsequent secuenciación.Se recommended study initiation by qPCR analysis, since deletions are the most common genetic abnormalities associated with Leri-Weill dyschondrosteosis.
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).