Mutations producing premature termination of translation and an amino acid substitution in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis associated with parkinsonism
| Autor: | Masataka Hayashi, Yasuo Gotoda, R Kondo, Toshio Matsumoto, Yoshihiko Nishida, Hisaomi Kawai, Shoji Tsuji, Hiroshi Kondo, Nobuaki Wakamatsu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1999 |
| Předmět: |
Adult
Nonsense mutation DNA Mutational Analysis Biology medicine.disease_cause Cerebrotendinous Xanthomatosis Cytochrome P-450 Enzyme System medicine Humans Gene Genetics chemistry.chemical_classification Mutation Transition (genetics) Parkinsonism Parkinson Disease Xanthomatosis Cerebrotendinous Middle Aged medicine.disease Stop codon Amino acid Psychiatry and Mental health chemistry Amino Acid Substitution Protein Biosynthesis Papers Steroid Hydroxylases Cholestanetriol 26-Monooxygenase Surgery Female Neurology (clinical) Polymorphism Restriction Fragment Length |
| Popis: | OBJECTIVES Mutational analysis of the sterol 27-hydroxylase ( CYP27 ) gene was performed on three patients from two Japanese families who had cerebrotendinous xanthomatosis (CTX) associated with parkinsonism. METHODS Clinical evaluations, brain MRI studies, and laboratory analyses were completed on the three patients. The CYP27 gene was analysed for mutations by PCR amplification of gene segments followed by direct sequencing. RESULTS Two different, homozygous mutations were identified in these families. One is a novel transition, substituting T for G at Glu162 (GAG) resulting in a stop codon (TAG). The other is also a transition, substituting T for C at Arg441 (CGG) resulting in Trp (TGG). The second is located in two amino acids ahead of the heme ligand binding site (Cys443) of the protein likely rendering it non-functional. It is the most common CTX mutation in Japanese patients. CONCLUSIONS CTX with parkinsonism is caused by mutations with a severe impact on enzyme function. The two mutations described here are likely to cause loss of function because they are chain terminating or affect an essential site in the protein. |
| Databáze: | OpenAIRE |
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