In addition, synonymous variants in 4 genes [(Cadherin Related 23 (CDH23), SLC9A3 Regulator 1 (SLC9A3R1), Rhomboid Domain Containing 2 (RHBDD2), and Inter-Alpha-Trypsin Inhibitor Heavy Chain 2 (ITIH2)] linked with alzheimer's disease warrant comprehensive scrutiny of genetic variations [21]. The gene discussed is ITIH2; the disease is early-onset autosomal dominant Alzheimer disease.