Extensive investigation of a large Brazilian pedigree of 11778/haplogroup J Leber hereditary optic neuropathy
| Autor: | Adriana Berezovsky, Rubens Belfort, Alfredo A. Sadun, Josenilson Martins Pereira, Rafael E. Andrade, Stan Schein, Angelo Passos, A.M. DeNegri, Patrícia K. Kjaer, Federico Sadun, Peter A. Quiros, Valerio Carelli, Milton Rocha Moraes, Solange Rios Salomão, Maria Lucia Valentino |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Heterozygote Mitochondrial DNA Lineage (genetic) Adolescent genetic structures DNA Mutational Analysis Visual Acuity Optic Atrophy Hereditary Leber DNA Mitochondrial Polymerase Chain Reaction Haplogroup Cohort Studies Contrast Sensitivity Risk Factors Humans Medicine Genetics business.industry Incidence (epidemiology) Haplotype Middle Aged Penetrance eye diseases Pedigree Ophthalmology Haplotypes Population study Female Visual Fields business Brazil Color Perception Cohort study |
| Zdroj: | American Journal of Ophthalmology. 136:231-238 |
| ISSN: | 0002-9394 |
| DOI: | 10.1016/s0002-9394(03)00099-0 |
| Popis: | To conduct systematic epidemiologic, neuro-ophthalmologic, psychophysical, and mitochondrial DNA (mtDNA) genetic examinations on a newly identified pedigree with Leber hereditary optic neuropathy (LHON).Observational population cohort study.A prospective investigation of an entire Brazilian LHON family.A field investigation by an international team conducted in a remote part of Brazil.We evaluated 265 (both eyes) of the 328 living family members of this LHON pedigree. Only members of this pedigree were studied. Those entering the pedigree as spouses were used as controls.We conducted epidemiologic interviews emphasizing possible environmental risk factors, comprehensive neuro-ophthalmologic examinations, psychophysical tests, Humphrey visual field studies, fundus photography, and blood testing for mitochondrial genetic analysis.We reconstructed a seven-generation maternal lineage descended from a common ancestor dating to the 1870s. All maternally related family members were invariably homoplasmic 11778 with a haplogroup J mtDNA, 33 being affected, of which 22 are still living. With each subsequent generation, there was a progressive decrease of penetrance, and only males were affected in the last two generations. A significant exposure (greater than 95% confidence intervals) to a variety of environmental risk factors characterized the affected individuals, with smoking as the most common (P.01). Both affected and carriers (95% confidence intervals) presented with a significantly lower incidence of hypertension and high cholesterol compared with the control group (P.05).Almost 95% of a 328-living-member pedigree with LHON 11778/J haplogroup was comprehensively studied. Our initial results indicate the strong influence of environmental risk factors. The remarkably reduced incidence of cardiovascular risk in the maternal lineage is discussed. Further genetic analysis may reveal a role for the nuclear genome. |
| Databáze: | OpenAIRE |
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