Frequency of rare mitochondrial DNA mutations in patients with suspected Leber's hereditary optic neuropathy
| Autor: | Douglass M. Turnbull, Robert W. Taylor, Patrick F. Chinnery, M S Jobling |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Genetics
congenital hereditary and neonatal diseases and abnormalities Mitochondrial DNA genetic structures Point mutation DNA Mutational Analysis Leber's hereditary optic neuropathy Respiratory chain nutritional and metabolic diseases Pedigree chart Optic Atrophy Hereditary Leber Biology medicine.disease DNA Mitochondrial eye diseases Optic neuropathy Atrophy Gene Frequency medicine Humans Point Mutation Online Mutation Report Allele frequency Genetics (clinical) |
| Zdroj: | Journal of Medical Genetics. 40:85e-85 |
| ISSN: | 1468-6244 |
| DOI: | 10.1136/jmg.40.7.e85 |
| Popis: | Leber’s hereditary optic neuropathy (LHON (MIM 535000)) characteristically presents with subacute painless bilateral visual failure in young adults, with a predilection for males.1,2 In the largest multicentre study of white people with LHON,3 97% of those affected were found to harbour one of three “primary” mitochondrial DNA (mtDNA) point mutations affecting genes that code for different subunits of complex I (NADH-ubiquinone oxidoreductase, or ND) of the respiratory chain, G11778A, G3460A, and T14484C, which affect the ND4,4 ND1,5,6 and ND6,7 subunits respectively. This work had profound implications for the clinical investigation of patients with suspected LHON, indicating that a simple molecular genetic blood test would confirm the diagnosis in 19 out of 20 cases, and that a negative result reduces the likelihood of LHON to less than 1 in 20. In the original multicentre study of Mackey et al ,3 cases were carefully selected to avoid the inclusion of pedigrees with autosomal dominant or autosomal recessive optic atrophy. The authors only analysed pedigrees where there were at least two affected people related through an unaffected woman, and most of the pedigrees spanned several generations displaying strict maternal inheritance.3 Although this approach enriched their cohort for definite cases of LHON, it reduced the likelihood of including small pedigrees, which account for up to a third of genetically confirmed cases of LHON.8 Several additional mtDNA sequence variants have been described in patients with LHON over the past 10 years. Some of these sequence changes are also found in healthy controls at a lower frequency than in cases of LHON,9–11 and the role … |
| Databáze: | OpenAIRE |
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