Familial Alzheimer's disease co-segregates with a Met146I1esubstitution in presenilin-1
P. Jørgensen
Bok Engelsk 1996
| Utgitt | 1996
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| Omfang | Side 281- 286
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| Opplysninger | The presenilin-1 (PS-1)/S 182 gene at chromosome 14q24.3 is, whenmutated, the most common disease gene in autosomal dominant early-onset Alzheimer's disease. Substitution of methionine 146 of the geneproduct for either valine or leucine co-segregates with Alzheimer'sdisease with the age of onset in the late thirties or early forties.Here we describe a new substitution of methionine 146 for isoleucinethat co-segregates with Alzheimer's disease with age of the onset inthe early forties. All identified missense mutations in methioninecodon 146 replace one hydrophobic amino acid (Met) with another (Val,Leu, lie) and correspond to any nucleotide change at the first orthird position of the codon. Second position mutations invariablylead to replacement of the hydrophobic methionine with a hydrophilicamino acid that may severely affect the function of the protein. Thefact that no second position mutations have been identified so farmay support the hypothesis that the protein product of PS-I plays acrucial role during development.
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