Mendelian inheritance of immunodeficiency disorders

Pedigree charts are used to analyze the inheritance of traits within a human population. If enough progeny data is available, careful analysis of the phenotypes can provide information about the genetic inheritance of a disease.

Immunodeficiency disorders are caused when the immune system’s ability to fight infectious disease is compromised. While immunodeficiency disorders vary widely, they are typically characterized by the person’s inability to make sufficient amounts of immune cells or by the production of immune cells that are mutated such that they cannot function properly. Given the wide variety of disorders, pedigree charts can be useful in determining what form of Mendelian inheritance a particular disease follows.

Bruton syndrome, is a rare genetic disorder that is characterized by a mutation in the Bruton’s tyrosine kinase gene, which blocks the ability of B-cells to develop. To better understand the inheritance patterns of Bruton’s syndrome, a family was followed for three generations (Figure 1).

Figure 1. Pedigree of family with cases of Bruton’s syndrome

Figure legend: Circles are female, squares are male, black-filled shapes indicate individuals with Bruton’s syndrome.

Another study followed a family with a different immunodeficiency disorder called hyper-IgE syndrome (Figure 2). There are several forms of hyper-IgE syndrome, which is characterized by mutations that prevents proper neutrophil chemotaxis. This disease results in recurrent cold infections, eczema-like skin rashes, and lung infections. In this pedigree, the hyper-IgE syndrome was characterized by a mutation in the STAT3 gene.

Figure 2. Pedigree of family with cases of hyper-IgE syndrome

Figure legend: Circles are female, squares are male, black-filled shapes indicate individuals with hyper-IgE syndrome.