| Autor: |
Puck, Jennifer M., Pepper, Amy E., Henthorn, Paula S., Candotti, Fabio, Isakov, Judith, Whitwam, Todd, Conley, Mary Ellen, Fischer, Roxanne E., Rosenblatt, Howard M., Small, Trudy N., Buckley, Rebecca H. |
| Zdroj: |
Blood; March 1997, Vol. 89 Issue: 6 p1968-1977, 10p |
| Abstrakt: |
Severe combined immunodeficiency (SCID) is a syndrome of profoundly impaired cellular and humoral immunity. In humans, SCID is most commonly caused by mutations in the X-linked gene IL2RG, which encodes the common γ chain, γc, of the leukocyte receptors for interleukin-2 and multiple other cytokines. To investigate the frequency and variety of IL2RG mutations that cause SCID, we analyzed DNA, RNA, and B-cell lines from a total of 103 unrelated SCID-affected males and their relatives using a combination of molecular and immunologic techniques. Sixty-two different mutations spanning all eight IL2RG exons were found in 87 cases, making possible correlations between mutation type and functional consequences. Although skewed maternal X chromosome inactivation, single-strand conformation polymorphism, mRNA expression, and cell surface staining with anti-γc antibodies were all helpful in establishing IL2RG defects as the cause of SCID, only dideoxy fingerprinting and DNA sequence determination each detected 100% of the IL2RG mutations in our series. Abnormal γc chains may be expressed in the lymphocytes of as many as two thirds of patients with X-linked SCID. Specific mutation diagnosis thus remains technically challenging, but it is important for genetic counseling and perhaps for helping to select appropriate subjects for retroviral gene therapy trials. |
| Databáze: |
Supplemental Index |
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