Langer mesomelic dysplasia (Langer mesomelic dysplasia) - Gene SHOX
The mesomelic Langer dysplasia is a rare disease characterized by severe and disproportionate short stature, with rhizomelic shortening and mesomelic of the upper and lower extremities. In addition, some affected people have Madelung deformity, which can cause pain and limit movement of the wrist and an underdeveloped lower jaw. This disease is homozygous form of Leri-Weill dyschondrosteosis - see Leri-Weill Dyschondrosteosis - SHOX- gene.
The Langer mesomelic dysplasia is caused by mutations in SHOX gene, located on the short arm of chromosome X 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. Genes in the pseudoautosomal region are present on both chromosomes. As a result, women who have two X chromosomes, and men, who have an X and a Y, having two functional copies of the gene in every cell SHOX.
Deletions in the SHOX gene are the most frequent change responsible for the disease. Other genetic changes in the SHOX can also cause disease, as deletions of genetic material nearby normally help regulate gene activity. These changes greatly reduce or eliminate the amount of protein that is encoded SHOX. The absence or deficiency of this protein alters the development and normal bone growth before birth.
The mesomelic dysplasia Langer has a pattern of recessive inheritance seudoautosómico. The SHOX gene is both chromosomes X and Y, in an area known as the pseudoautosomal region. Although many genes are unique in either the X or Y chromosome genes in the region pseudoautosomal they are present in both sex chromosomes. The inheritance pattern of Langer mesomelic dysplasia described as recessive since both copies of the gene in every cell SHOX should be absent or altered 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 in IVAMI: in IVAMI perform detection of mutations associated with Langer mesomelic dysplasia, 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) if postnatal diagnosis. Prenatal diagnosis amniotic liquid.