Which best describes the genetic basis of DiGeorge syndrome as given in the material?

• A. A chromosomal duplication on chromosome 22
• B. A deletion on chromosome 22
• C. A point mutation in CFTR gene
• D. A translocation involving chromosome 22

Answer: (B)

DiGeorge syndrome is produced by a loss of genetic material in a specific region of chromosome 22, known as a microdeletion at 22q11.2. This deletion reduces the dosage of several genes in that region, including TBX1, leading to the characteristic features such as thymic hypoplasia, hypoparathyroidism, and heart defects due to disrupted development. Because the issue is a deletion, not an extra copy, the problem is inadequate gene function from one copy rather than overexpression. A chromosomal duplication on chromosome 22 would create a different condition with different effects. A point mutation in the CFTR gene causes cystic fibrosis, unrelated to 22q11.2 deletion. A translocation involving chromosome 22 could disturb genes but does not describe the classic 22q11.2 microdeletion responsible for DiGeorge. Most cases arise as a de novo deletion in 22q11.2, detectable with targeted testing like FISH or microarray.