Alpha-1 Antitrypsin Deficiency PiZZ

A 42-year-old never-smoking woman with progressive dyspnea, chronic cough, and recurrent bacterial pneumonia is found to have panacinar emphysema with lower-lobe predominance on CT chest. Serum alpha-1 antitrypsin (AAT) level is 24 mg/dL (normal 100–200 mg/dL), and Pi phenotyping shows PiZZ genotype. Her parents are both asymptomatic PiMZ heterozygotes with AAT levels around 60% of normal. Her older brother is PiMM (unaffected), and her younger sister is PiZZ but remains asymptomatic at age 38. The inheritance pattern shown in the pedigree, marked **C**, demonstrates which of the following principles?