A 12-year-old girl with progressive cerebellar ataxia, oculocutaneous telangiectasias, recurrent sinopulmonary infections, and selective IgA deficiency is found to have an elevated alpha-fetoprotein. The underlying genetic defect lies in a gene whose product normally functions in:

• A Actin polymerization in hematopoietic and platelet cytoskeletons
• B Repairing double-stranded DNA breaks via homologous recombination ✓
• C Class switching recombination in germinal center B cells
• D Thymic epithelial development and parathyroid organogenesis

Explanation

Ataxia-telangiectasia results from mutations in the ATM gene, encoding a kinase central to detecting double-stranded DNA breaks and coordinating repair checkpoints. Loss of ATM causes cerebellar Purkinje cell degeneration, vascular telangiectasias, immunodeficiency with low IgA and IgG subclasses, chromosomal instability, and marked sensitivity to ionizing radiation, along with raised AFP and increased lymphoid malignancy risk. Actin polymerization defines Wiskott-Aldrich syndrome, and thymic development defines DiGeorge syndrome.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.