Linked Life Data

16923955

Source:http://linkedlifedata.com/resource/pubmed/id/16923955

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 9
pubmed:dateCreated
2006-8-22
pubmed:abstractText
By far the largest known kindred with an inherited prion disease caused by a prion protein (PrP) octapeptide repeat insertion mutation originates from southeast England. This extended family shows very marked phenotypic heterogeneity and provides a unique opportunity to characterize this diversity and examine possible modifying factors amongst a large number of individuals in whom prion disease has been initiated by the same defined genetic mutation. As the inherited prion diseases comprise a significant proportion of familial early-onset dementia, an appreciation of their wide range of clinical presentation is important for differential diagnosis. Genealogical and clinical record review, together with the characterization of the mutation-linked single nucleotide polymorphism and microsatellite haplotype, suggested a single founder for both this large kindred and a smaller family in the mid-18th century. Here we report the phenotype of 86 affected individuals; at least another 84 individuals are known to be at risk of inheriting the disease. Clinical onset, typically with cognitive impairment, can be strikingly early in this kindred when compared with other inherited or sporadic prion diseases. We have investigated the effect of PrP genotype, candidate genes and prion strain type on clinical, neuroradiological and neuropathological phenotype. The transmission characteristics of prions from affected individuals resembled those of classical sporadic Creutzfeldt-Jakob disease. One surprising finding was a strong inverse correlation between age of onset and disease duration. The PrP gene polymorphic codon 129 was found to confer 41% of the variance in age of onset but interestingly this polymorphism had no effect on disease duration suggesting different molecular mechanisms are involved in determining disease onset and rate of clinical progression.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1460-2156
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
129
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2297-317
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16923955-Adult, pubmed-meshheading:16923955-Age of Onset, pubmed-meshheading:16923955-Apolipoproteins E, pubmed-meshheading:16923955-Codon, pubmed-meshheading:16923955-DNA Transposable Elements, pubmed-meshheading:16923955-Family Health, pubmed-meshheading:16923955-Female, pubmed-meshheading:16923955-Haplotypes, pubmed-meshheading:16923955-Humans, pubmed-meshheading:16923955-Male, pubmed-meshheading:16923955-Microsatellite Repeats, pubmed-meshheading:16923955-Middle Aged, pubmed-meshheading:16923955-Mutagenesis, Insertional, pubmed-meshheading:16923955-Mutant Proteins, pubmed-meshheading:16923955-Mutation, pubmed-meshheading:16923955-Pedigree, pubmed-meshheading:16923955-Peptides, pubmed-meshheading:16923955-Phenotype, pubmed-meshheading:16923955-Polymorphism, Single Nucleotide, pubmed-meshheading:16923955-PrPSc Proteins, pubmed-meshheading:16923955-Prion Diseases, pubmed-meshheading:16923955-Prions, pubmed-meshheading:16923955-Sex Factors, pubmed-meshheading:16923955-Time Factors
pubmed:year
2006
pubmed:articleTitle
Inherited prion disease with six octapeptide repeat insertional mutation--molecular analysis of phenotypic heterogeneity.
pubmed:affiliation
MRC Prion Unit, Department of Neurodegenerative Diseases, Institute of Neurology, King's College Hospital, London, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't