This was not as much of a problem in males, but in female carriers, where the fragile site could generally only be seen in 10% of cells, the mutation often could not be visualised.Since the 1990s, more sensitive molecular techniques have been used to determine carrier status. The fragile X abnormality is now directly determined by analysis of the number of CGG repeats using polymerase chain reaction (PCR) and methylation status using Southern blot analysis. By determining the number of CGG repeats on the X chromosome, this method allows for more accurate assessment of risk for premutation carriers in terms of their own risk of fragile X associated syndromes, as well as their risk of having affected children. Because this method only tests for expansion of the CGG repeat, individuals with FXS due to missense mutations or deletions involving FMR1 will not be diagnosed using this test and should therefore undergo sequencing of the FMR1 gene if there is clinical suspicion of FXS.Prenatal testing with chorionic villus sampling or amniocentesis allows diagnosis of FMR1 mutation while the fetus is in utero and appears to be reliable.Early diagnosis of fragile X syndrome or carrier status is important for providing early intervention in children or fetuses with the syndrome, and allowing genetic counselling with regards to the potential for a couples future children to be affected. Most parents notice delays in speech and language skills, difficulties in social and emotional domains as well as sensitivity levels in certain situations with their children.
Hypergammaglobulinemia is a medical condition with elevated levels of gamma globulin. It is a type of immunoproliferative disorder. Types
Hypergammaglobulinemia is a condition that is characterized by the increased levels of a certain immunoglobulin in the blood serum. The name of the disorder refers to an excess of proteins after serum protein electrophoresis (found in the gammaglobulin region).Most hypergammaglobulinemias are caused by an excess of immunoglobulin M (IgM), because this is the default immunoglobulin type prior to class switching. Some types of hypergammaglobulinemia are actually caused by a deficiency in the other major types of immunoglobulins, which are IgA, IgE and IgG. There are 5 types of hypergammaglobulinemias associated with hyper IgM.MeSH considers hyper IgM syndrome to be a form of dysgammaglobulinemia, not a form of hypergammaglobulinemia. Type 1
X-linked immunodeficiency with hyper–immunoglobulin M, which is also called type 1 hyper IgM, is a rare form of primary immunodeficiency disease caused by a mutation in the Tumor Necrosis Factor Super Family member 5 (TNFSF5) gene, which codes for CD40 ligand. This gene is located on the long arm of the X chromosome at position 26, denoted Xq26. Normally, CD40 ligand is expressed on activated T cells, and is necessary to induce immunoglobulin class switching from IgM to the other immunoglobulin types. It does this by binding to its ligand, CD40, which is found expressed on the surface of B cells.