Age dependent penetrance of three different superoxide dismutase 1 (sod 1) mutations.

摘要

The age of onset of motor neuron disease in Cu/Zn superoxide dismutase 1 (SOD1) mutation carriers are variable, commencing at any time from the second decade. The authors performed a retrospective analysis of family information in pedigrees dating back to the 1780s, to determine the age-dependent penetrance of three different SOD1 mutations: Glu100Gly, Ile113Thr, and Val148G1y. The penetrance of symptomatic MND in these three SOD1 mutations was greater than 95% by the age of 78. The affected family members with the Val148Gly mutation had the worst prognosis, with a mean age of death of 46.1 years, compared to 54.2 years for the Glu100Gly mutation and 59.9 years for Ile113Thr mutation. Kaplan-Meier survival curves showed that survival of the 3 SOD1 mutation families, when combined, was reduced by nearly 10 years with the mean age of death for all SOD1 mutation carriers being 52.6 years compared to 62.5 years for the control individuals. The SOD1 mutation group also resulted in earlier death compared to sporadic MND, which from natural history studies is 61.4 years. This may reflect that the SOD1 mutation is associated with more progressive and rapid disease, as the age of onset of disease was not earlier. This information would have important implications for genetic counseling of members of individual SOD1 mutation carrier families.