rs121908120

Whole genome sequencing of 44 Ashkenazi Jewish centenarians identified 216 coding variants annotated as pathogenic or likely pathogenic in ClinVar. The study found 130 rare variants (MAF <5%) reported to cause degenerative, neoplastic, and cardiac diseases with various inheritance patterns. Notably, several carriers had no clinical manifestations despite carrying variants linked to serious diseases (e.g., an APOE ε4 homozygote without Alzheimer's disease, a UBQLN2 P525S carrier without ALS). These findings suggest incomplete penetrance and reduced clinical significance for many reported disease mutations.

A family report of isolated hypodontia (missing and small teeth) caused by two WNT10A missense mutations: c.682T>A (p.Phe228Ile) and c.649G>A (p.Asp217Asn). The father and oldest son carried the first mutation, the mother and second son carried the second mutation, and the youngest son was a compound heterozygote. No other features of ectodermal dysplasia were observed, demonstrating that WNT10A mutations can cause isolated hypodontia without systemic manifestations.