Congenital Immunodeficiency Genetics

  1. Three congenital immunodeficiency:
    • SCID
    • DiGeorge
    • Bruton/X-linked agammaglobulinemia
  2. DiGeorge is a genetic mutation in the development of _____ cells. SCID is a genetic mutation in the development of _____ cells. Bruton/X-linked Agammaglobulinemia is a genetic mutation in the development of _____ cells.
    • T
    • T or B (B cell is d/t VDJ inhibition)
    • B
  3. Which congenital immunodeficiency is due to the absence of a thymus?
    DiGeorge Syndrome
  4. Which congenital immunodeficiency is due to inhibition of VDJ recombination in both B and T cell receptors?
    SCID (due to defects in Pre-B and T cell receptors RAG 1 and RAG2)
  5. Which congenital immunodeficiency is due to early mutation inhibiting the differentiation and activation of T cells?
    SCID (X-linked)
  6. Which congenital immunodeficiency is due to BTK mutations affecting pre-B cell maturation to mature B cells?
    XLA (X-linked agammaglobulinemia)
  7. T/F: SCID is sometimes caused by defects that completely abrogate the development of B lymphocytes
    True; thought most of the time is the absence of T lymphocytes development! Sometimes, it could also affect NK lymphocytes
  8. A young pt presents with severe infections, protracted diarrhea and failure to thrive:
    Think SCID
  9. What is mutated in X-linked SCID, and what is the result of that mutation?
    X-linked recessive mutation of IL2RG genes which codes for gamma chain of many interleukin receptors, notably IL-7 (T cell maturation), IL-2 (T cell activation) and IL-15 (NK cell activation)
  10. What is the inheritance pattern of the SCID that is deficient in adenosine deaminase?
    Autosomal recessive
  11. What happens with ADA deficiency SCID?
    Adenosine deaminase is not present to break down purines, causing accumulation of dATP which inhibits DNA synthesis and T and B cells are very much mitotically active so they get heavily affected as a result
  12. T/F: X-linked recessive SCID is due to mutation of the RAG1 and RAG2 genes
    False; X-linked recessive SCID is due to mutation of IL2RG. The autosomal recessive defects in the pre-T cell receptor is due to mutation of RAG1 and RAG2
  13. What is the significance of RAG1 and RAG2 genes?
    Initiate the VDJ recombination process ultimately enabling generation of B and T cells with a diversified repertoire of antigen-specific receptors
  14. What is the chromosomal deletion seen in DiGeorge Syndrome?
    • 22q11 deletion with 30-50 genes, notably TBX 1, CATCH 22 cardiac defects
    • Causing developmental anomalies of the third and fourth pharyngeal pouches characterized by thymic hypoplasia.
  15. What are some anatomic and physiologic defects seen in DiGeorge syndrome?
    • Heart defects (CATCH 22)
    • Abnormal facial features
    • Absent parathyroid
    • Cleft palate
    • Thymic hypoplasia
    • Microcephaly
    • Speech delay
    • Neurobehavioral problems
  16. What is the inheritance pattern of DiGeorge syndrome?
    • Autosomal DOMINANT
    • Most patients have “partial DGS” manifested by mild T-cell lymphopenia and immunodeficiency
  17. A two-year old with DiGeorge syndrome presents with seizures. What is expected on his lab report with regards to parathyroid and calcium levels?
    • Both low
    • Due to defects of the parathyroid
  18. What is mutated in XLA?
    Bruton’s tyrosine kinase (BTK) gene which causes failure of B cell development
  19. T/F: XLA affects both T and B cell immunity
    False; T cell immunity is intact in XLA, only B cell is affected
  20. What are the 3 genetic causes of SCID?
    • IL2RG (X-linked)
    • RAG1 RAG 2 (autosomal recessive)
    • ADA deficiency (autosomal recessive)
  21. Which gene is important in the expression of a large variety of interleukin receptors?
    • IL2RG
    • It is the gene coding for the gamma chain of interleukin receptors
  22. What is the mechanism by which antibody production is inhibited in patients with RAG deficiency?
    absence of VDJ recombination
  23. What is the cause of absent B cells in agammaglobulinemia?
    BTK mutation
Card Set
Congenital Immunodeficiency Genetics
HemeOnc Midterm 2