1. The purpose of this study is to learn more about the changes in genes, cells and proteins that cause immune deficiency diseases.

2. The early stages of the study will focus on two groups of patients:

   1. members of families in which several persons have symptoms or medical histories that suggest immune deficiency.
   2. Patients who have received treatments with medications or drugs that affect functions of the immune system (secondary immune deficiencies).

It is hoped that studies will provide guidelines for extension of the research to other patient groups. Up to 200 patients and family members will be invited to participate.

The experiments that are proposed in this portion of the study are intended to:

1. characterize the significance of the variant form of EZH2 identified in this family. They will characterize the degree of methylation of lysine 27 of histone H3 in subjects with the variant and members of the same family who have the wild type gene. The functional methyltransferase activity of the variant and wild type genes will be measured.
2. characterize the current status of B-cell maturation and function in subjects with either the variant gene and the wild type gene.
3. characterize B-cell function (antibody production) and the quality of antibody produced after immunizations in subjects with the wild type gene or the variant gene.

Inclusion Criteria:

1. Immunodeficiency disease; or
2. family member of individual with immunodeficiency disease

Exclusion Criteria:

1. Persons with immune deficiencies that are secondary to other diseases such as malignancies.
2. Persons who do not have immune deficiencies, persons who are not meet eligibility criteria

Individuals aged 18 years or older and have an immune deficiency or are related to a person who has an immune deficiency.