Current opinion in immunology
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Curr. Opin. Immunol. · Feb 2015
ReviewImmunological loss-of-function due to genetic gain-of-function in humans: autosomal dominance of the third kind.
All the human primary immunodeficiencies (PIDs) recognized as such in the 1950s were Mendelian traits and, whether autosomal or X-linked, displayed recessive inheritance. The first autosomal dominant (AD) PID, hereditary angioedema, was recognized in 1963. However, since the first identification of autosomal recessive (AR), X-linked recessive (XR) and AD PID-causing genes in 1985 (ADA; severe combined immunodeficiency), 1986 (CYBB, chronic granulomatous disease) and 1989 (SERPING1; hereditary angioedema), respectively, the number of genetically defined AD PIDs has increased more rapidly than that of any other type of PID. ⋯ Malignancies are also rare. The enormous diversity of immunological and clinical phenotypes is thought provoking and mirrors the diversity and pleiotropy of the underlying genotypes. These experiments of nature provide a unique insight into the quantitative regulation of human immunity.