Rothmund-Thomson Syndrome

A 4-year-old girl born to consanguineous parents presents with a distinctive rash that began at 4 months of age on the cheeks and progressed to the extensor surfaces. Over time, the rash has evolved into a mottled appearance with hypopigmented and hyperpigmented macules, telangiectasias, and atrophic patches. She has sparse fine hair with absent eyelashes and eyebrows, dystrophic nails, short stature with bilateral absent thumbs and hypoplastic radii, juvenile cataracts, and a family history of osteosarcoma in her older brother and squamous cell carcinoma in a maternal cousin. Karyotype analysis reveals the finding marked **A** in the diagram. Which of the following best explains the genomic instability and cancer predisposition in this patient?