Question

Prenatal diagnosis of hemophilia is best done by:

• A. PCR
• B. Linkage analysis
• C. Cytometry
• D. Microarray

Hint:

Known single-gene mutation in fetal DNA is best confirmed by direct amplification.

Answer 1

The Correct Option is A

Step 1: Recall the genetics of hemophilia. Hemophilia A (factor VIII) and hemophilia B (factor IX) are X-linked recessive single-gene disorders. Prenatal diagnosis aims to detect the disease-causing mutation in fetal DNA.
Step 2: Consider direct mutation detection. When the specific mutation in the family is known, PCR-based direct mutation analysis amplifies the relevant region of the factor VIII or factor IX gene and identifies the mutation in chorionic villus or amniotic fluid DNA. This is the most accurate and definitive approach, including detection of the common intron 22 inversion in severe hemophilia A by PCR-based methods.
Step 3: Compare the alternatives. Linkage analysis using PCR-based polymorphic markers is used as an indirect method only when the family mutation is unknown, and it requires informative relatives and carries recombination error; it is a fallback, not the best. Flow cytometry measures cell surface markers and DNA content, not point mutations in a coagulation gene. Microarray detects copy-number changes, not the small mutations typical of hemophilia.
Step 4: Because direct PCR-based mutation detection is the most precise and is the test of choice for prenatal diagnosis of a known single-gene disorder, the answer is PCR (option A).