PURPOSE: To report on an investigation of the largest pedigree ever extensively evaluated with Leber’s Hereditary Optic Neuropathy (LHON), and to provide results of genetic testing, neuro-eye evaluations, dietary and social profiles as well as environmental exposures.
METHODS: Based upon the advice of two of its founding members (Sherman, Bodis-Wollner), the International Foundation of Optic Nerve Disease (IFOND) sponsored two field studies in a remote section of Brazil. The teams included Drs. Belfort, Salomao, and Berezovsky from the Federal University of Sao Paulo, Brazil who evaluated several patients in a pilot study and confirmed LHON. The family came to the attention of IFOND because of an e-mail to the IFOND website from the mother of a 14 yo male with a family history of blindness who recently lost vision. Over 300 family members were evaluated on the first field trip (Oct 2001) and the second is scheduled in Oct 2002. Blood samples have been evaluated by team member, V. Carelli, from the University of Bologna, Italy.
RESULTS: All tested subjects were homoplasmic for the mitochondrial mutation 11778. Thirty three family members were blind (20/400-LP) and 150 are at risk of blindness. A woman from Verona, Italy, who immigrated to Brazil in 1861 was the earliest member of this 8 generation, 300 member pedigree. The subsequent generations demonstrated a gradual decreasing penetrance rate of 71% to 9%. Age of onset of visual loss ranged from 10-64 years. In addition to the mutation at 11778, nuclear genetic linkage and epi-genetic findings likely contribute to the blindness.
CONCLUSIONS: A database of over 300 subjects with LHON has been established as well as analysis of environmental factors and a search for a nuclear modifying gene. This database provides a unique opportunity for clinical trials of presently unaffected subjects of any purported neuro-protective agent.