Mutations in the gene encoding peroxisomal alpha-methylacyl-CoA racemase cause adult-onset sensory motor neuropathy
| Autor: | R. J. A. Wanders, Simone Denis, Peter E. Clayton, Brendan McLean, Hans R. Waterham, Ann Y. Brown, J. T. Allen, J. E. Rees, A. Graham, Peter Vreken, Sacha Ferdinandusse |
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| Přispěvatelé: | Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
Adult
Male Pristanic acid medicine.medical_specialty Molecular Sequence Data Racemases and Epimerases Biology Alpha-methylacyl-CoA racemase medicine.disease_cause Biochemistry Mice chemistry.chemical_compound Internal medicine α methylacyl coa racemase Escherichia coli Peroxisomes Genetics medicine Animals Humans Point Mutation Amino Acid Sequence Age of Onset Cloning Molecular Gene Sensory motor Mutation Sequence Homology Amino Acid Point mutation Infant AMACR Gene Middle Aged Peroxisome medicine.disease Molecular biology Recombinant Proteins Rats Refsum disease Endocrinology Amino Acid Substitution chemistry Female Adrenoleukodystrophy Hereditary Sensory and Motor Neuropathy Sequence Alignment |
| Zdroj: | Nature genetics, 24(2), 188-191. Nature Publishing Group |
| ISSN: | 1061-4036 |
| Popis: | Sensory motor neuropathy is associated with various inherited disorders including Charcot-Marie-Tooth disease, X-linked adrenoleukodystrophy/adrenomyeloneuropathy and Refsum disease. In the latter two, the neuropathy is thought to result from the accumulation of specific fatty acids. We describe here three patients with elevated plasma concentrations of pristanic acid (a branched-chain fatty acid) and C27-bile-acid intermediates. Two of the patients suffered from adult-onset sensory motor neuropathy. One patient also had pigmentary retinopathy, suggesting Refsum disease, whereas the other patient had upper motor neuron signs in the legs, suggesting adrenomyeloneuropathy. The third patient was a child without neuropathy. In all three patients we discovered a deficiency of alpha-methylacyl-CoA racemase (AMACR). This enzyme is responsible for the conversion of pristanoyl-CoA and C27-bile acyl-CoAs to their (S)-stereoisomers, which are the only stereoisomers that can be degraded via peroxisomal beta-oxidation. Sequence analysis of AMACR cDNA from the patients identified two different mutations that are likely to cause disease, based on analysis in Escherichia coli. Our findings have implications for the diagnosis of adult-onset neuropathies of unknown aetiology. |
| Databáze: | OpenAIRE |
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