Question

Neurofibromatosis type 1 (NFl: also known as von Recklinghausen disease) is an inherited dominant disorder. The phenotype usually involves the production of many skin neurofibromas (benign tumors of the fibrous cells that cover the nerves). a. Is it likely that NF1 is a tumor-suppressor gene or an oncogene? b. Are the NFI neurofibromatosis-causing mutations that are inherited by affected children from affected parents likely to be loss-of-function or gain-of-function mutations? c. Neurofibromin, the protein product of NF1, has been found to be associated with the Ras protein. Ras is involved in the transduction of extracellular signals from growth factors. The active form of Ras (the form initiating the signal transduction cascade causing proliferation) is complexed with GTP; the inactive form of Ras is complexed with GDP. Would the wild-type neurofibromin protein favor the formation of Ras-GTP or Ras-GDP? d. Which of the following events in a normal cell from an individual inheriting a neurofibromatosis-causing allele could cause the descendants of that cell to grow into a neurofibroma? i. A second point mutation in the allele of NF1 inherited from the afflicted parent ii. A point mutation in the allele of NF1 inherited from the normal parent iii. A large deletion that removes the NF1 gene from the chromosome inherited from the afflicted parent iv. A large deletion that removes the NF1 gene from the chromosome inherited from the normal parent v. Mitotic chromosomal nondisjunction or chromosome loss vi. Mitotic recombination in the region between the NFl gene and the centromere of the chromosome carrying NFl vii. Mitotic recombination in the region between the NF1 gene and the telomere of the chromosome carrying NFl. e. A much rarer form of neurofibromatosis exists called segmental neurofibromatosis. In this form of the disease, neither parent of the patient has any clinical sign of the disease. The tumors in the patient are restricted to one part of the body, like the right leg. Suggest an explanation for the genesis of segmental neurofibromatosis that clarifies why it is restricted to one part of the body.

Answer 1

a. Neurofibromatosis type 1 (NF1) is likely an oncogene and

b. Neurofibromatosis type 1 (NF1) is associated with loss-of-function mutations.

c. The wild-type neurofibromin protein favors the formation of Ras-GTP.

d. A large deletion in the chromosome inherited from the afflicted parent is most likely to cause the growth of neurofibromas, hence answer is option iii.

e. Segmental neurofibromatosis may be explained by somatic mosaicism.

Step-by-step explanation:

a. Neurofibromatosis type 1 (NF1) is likely an oncogene as it leads to the production of many tumors.

b. The neurofibromatosis-causing mutations inherited from affected parents are most likely loss-of-function mutations as they result in the production of nonfunctional or reduced-function neurofibromin protein.

c. The wild-type neurofibromin protein would favor the formation of Ras-GTP.

d. Among the given events, a large deletion that removes the NF1 gene from the chromosome inherited from the afflicted parent is most likely to cause the descendants of the cell to grow into a neurofibroma, hence answer is option iii.

e. The genesis of segmental neurofibromatosis being restricted to one part of the body may be due to somatic mosaicism, which occurs when there is a mutation in the early stages of embryonic development.