Bloom Syndrome

A 6-year-old boy of Ashkenazi Jewish descent presents with severe short stature (height 100 cm), photosensitive malar telangiectatic erythema, and recurrent sinopulmonary infections. Cytogenetic analysis reveals the abnormality marked **B** in the diagram — quadriradial chromosomal configurations with a 10-fold increase in sister chromatid exchanges. Which of the following molecular defects best explains this cytogenetic finding?

A 7-year-old girl of Ashkenazi Jewish ancestry presents with severe proportionate dwarfism, microcephaly, and a photosensitive malar butterfly rash since infancy. She has recurrent infections, early-onset type 2 diabetes, and a family history of early malignancy (uncle with AML at age 23, aunt with colorectal cancer at age 31). Cytogenetic analysis with BrdU incorporation and Harlequin staining is performed. The finding marked **A** in the diagram—a striking increase in sister chromatid exchanges (92 per cell, >10-fold above normal) with quadriradial figures at homologous chromosome sites—is pathognomonic for which genetic defect?