DNA repair deficiency syndromes — MCQs

A 24-year-old man comes to the physician because his vision has worsened rapidly over the last 2 months. His maternal uncle lost his vision suddenly over a period of 3 months at 26 years of age. The patient's wife and 1-year-old son have normal vision. Funduscopic examination of the patient shows bilateral circumpapillary telangiectasia. Genetic testing shows a missense mutation in one of the genes of the electron transport chain complexes. The probability that this patient's son will be affected by the same disease is closest to which of the following?

A 7-month-old boy presents to the family physician with extensive scaliness and pigmentation of sun-exposed skin areas. His mother says that these symptoms were absent until mid-spring and then became significantly worse after their trip to California in the summer. The child was born in December to a consanguineous couple after an uncomplicated pregnancy. He is breastfed and receives mashed potatoes, bananas, and carrots as complementary foods. His weight is 8.5 kg (18.7 lb) and length is 70 cm (2 ft 96 in). The patient’s vital signs are within normal limits for his age. On physical examination, there is freckling, scaling, and erythema on the sunlight-exposed areas of the face, trunk, and upper and lower extremities. No blistering, scarring, hypertrichosis, or alopecia is noted. The rest of the exam is unremarkable. Which process is most likely disrupted in this patient?

A 47-year-old man presents to his primary care physician for fatigue. Over the past 3 months, his tiredness has impacted his ability to work as a corporate lawyer. He denies any changes to his diet, exercise regimen, bowel movements, or urinary frequency. His past medical history is notable for obesity, type II diabetes mellitus, and hypertension. He takes metformin and enalapril. His family history is notable for colorectal cancer in his father and paternal grandfather and endometrial cancer in his paternal aunt. He has a 20-pack-year smoking history and drinks one 6-pack of beer a week. His temperature is 98.8°F (37.1°C), blood pressure is 129/71 mmHg, pulse is 82/min, and respirations are 17/min. On exam, he has conjunctival pallor. A stool sample is positive for occult blood. A colonoscopy reveals a small hemorrhagic mass at the junction of the ascending and transverse colon. Which of the following processes is likely impaired in this patient?

While performing a Western blot, a graduate student spilled a small amount of the radiolabeled antibody on her left forearm. Although very little harm was done to the skin, the radiation did cause minor damage to the DNA of the exposed skin by severing covalent bonds between the nitrogenous bases and the deoxyribose sugar, leaving several apurinic/apyrimidinic sites. Damaged cells would most likely repair these sites by which of the following mechanisms?

A 44-year-old man comes to the physician because of fatigue and increased straining during defecation for 3 months. During this time, he has lost 5 kg (12 lb) despite no change in appetite. He has a family history of colon cancer in his maternal uncle and maternal grandfather. His mother died of ovarian cancer at the age of 46. Physical examination shows conjunctival pallor. His hemoglobin concentration is 11.2 g/dL, hematocrit is 34%, and mean corpuscular volume is 76 μm3. Colonoscopy shows an exophytic mass in the ascending colon. Pathologic examination of the resected mass shows a poorly differentiated adenocarcinoma. Genetic analysis shows a mutation in the MSH2 gene. Which of the following is the most likely diagnosis?

Two healthy adults have only one child. He has Friedreich ataxia (FA). They are considering having more children, but are uncertain of their risk of having another child with the condition. What should they do?

A 54-year-old woman with breast cancer comes to the physician because of redness and pain in the right breast. She has been undergoing ionizing radiation therapy daily for the past 2 weeks as adjuvant treatment for her breast cancer. Physical examination shows erythema, edema, and superficial desquamation of the skin along the right breast at the site of radiation. Sensation to light touch is intact. Which of the following is the primary mechanism of DNA repair responsible for preventing radiation-induced damage to neighboring neurons?

A 5-year-old girl is brought to the physician by her mother because of a 1-month history of a painful ulcer on her face. She has developed painful sunburns in the past with minimal UV exposure. Examination of the skin shows a 2-cm ulcerated nodule on the left cheek. There are scaly, hyperpigmented papules and plaques over the skin of the entire body. Ophthalmologic examination shows decreased visual acuity, clouded corneas, and limbal injection. Examination of a biopsy specimen from the facial lesion shows poorly-differentiated squamous cell carcinoma. Impairment of which of the following proteins is the most likely cause of this patient's condition?

A 3-year-old male child is found to have a disease involving DNA repair. Specifically, he is found to have a defect in the endonucleases involved in the nucleotide excision repair of pyrimidine dimers. Which of the following is a unique late-stage complication of this child's disease?

An investigator studying DNA mutation mechanisms isolates single-stranded DNA from a recombinant bacteriophage and sequences it. The investigator then mixes it with a buffer solution and incubates the resulting mixture at 70°C for 16 hours. Subsequent DNA resequencing shows that 3.7 per 1,000 cytosine residues have mutated to uracil. Which of the following best describes the role of the enzyme that is responsible for the initial step in repairing these types of mutations in living cells?