Extenive invetigation of a large Brazilian pedigree of 11778/haplogroup J Leber hereditary optic neuropathy

Purpoe To conduct ytematic epidemiologic, neuro-ophthalmologic, pychophyical, and mitochondrial DNA (mtDNA) genetic examination on a newly identified pedigree with Leber hereditary optic neuropathy (LHON). Deign Obervational population cohort tudy. Method A propective invetigation of an entire Brazilian LHON family. etting A field invetigation by an international team conducted in a remote part of Brazil. tudy population We evaluated 265 (both eye) of the 328 living family member of thi LHON pedigree. Only member of thi pedigree were tudied. Thoe entering the pedigree a poue were ued a control. Obervation procedure We conducted epidemiologic interview emphaizing poible environmental rik factor, comprehenive neuro-ophthalmologic examination, pychophyical tet, Humphrey viual field tudie, fundu photography, and blood teting for mitochondrial genetic analyi. Reult We recontructed a even-generation maternal lineage decended from a common ancetor dating to the 1870. All maternally related family member were invariably homoplamic 11778 with a haplogroup J mtDNA, 33 being affected, of which 22 are till living. With each ubequent generation, there wa a progreive decreae of penetrance, and only male were affected in the lat two generation. A ignificant expoure (greater than 95% confidence interval) to a variety of environmental rik factor characterized the affected individual, with moking a the mot common (P < .01). Both affected and carrier (95% confidence interval) preented with a ignificantly lower incidence of hypertenion and high choleterol compared with the control group (P < .05). Concluion Almot 95% of a 328-living-member pedigree with LHON 11778/J haplogroup wa comprehenively tudied. Our initial reult indicate the trong influence of environmental rik factor. The remarkably reduced incidence of cardiovacular rik in the maternal lineage i dicued. Further genetic analyi may reveal a role for the nuclear genome.