0
A 2 1 -year-old man is seen in the hematology clinic For evaluation of pancytopenia. The onset was noted at age 1 2 . and the course has been progressive. Current leukocyte count is 2.1 00/ JLL. hemoglobin 8.LJ g/dl with MCV 98 FL. and platelet count 29.000/ JLL. Reticulocyte percen tage is decreased at 1 .2% of red blood cel ls. On physical exam. he is noted to have short stature and multiple cafe-au-lait spots. While shaki ng his hand. you note that he has no thumb. The peri pheral blood smear and bone marrow biopsy are shown below.
What is the underlying pathophysiologic mechanism of FA?
- Defective mismatch repair genes
- Abnormal chromosomal breakage
- Dysregulation of telomerase
- Faulty mitotic spindle formation
Medicine
B. The primary molecular defect underlying FA is that cells derived from FA patients dis-play hypersensitivity to DNA cross-linking agents, such as mitomycin-C and diepoxybutane, causing chromosomal breakage. The FA pathway is composed of at least 15 genes, and multiple genes have been identified as defective in patients with FA, the most common being FA-A, located on chromo-some 16. Mismatch repair defects are seen in some types of colorectal cancer. Telomerase function is defective in dyskeratosis congenita. Mitotic spindle stabilization may play a role in the pathophysio-logic mechanism of Scwachman-Diamond syndrome, but this is not well understood.
need an explanation for this answer? contact us directly to get an explanation for this answer