Tangier's Disease (ABCA1, Autosomal Recessive)

A 14-year-old boy born to consanguineous first-cousin parents from the Middle East presents with bilateral orange-yellow tonsils, progressive distal sensory loss in a glove-and-stocking distribution, and mild intrinsic hand muscle weakness. Laboratory studies reveal extraordinarily low HDL cholesterol (4 mg/dL), undetectable apolipoprotein A-I, and foam cells on blood smear. A three-generation pedigree shows both the proband and his 11-year-old sister affected, while both parents and all grandparents are unaffected but have mildly reduced HDL levels (25–35 mg/dL). The pattern of inheritance shown in the pedigree marked as **A** is most consistent with which genetic mechanism?