NR ANXN
AU Del Bo,R.; Comi,G.P.; Giorda,R.; Crimi,M.; Locatelli,F.; Martinelli-Boneschi,F.; Pozzoli,U.; Castelli,E.; Bresolin,N.; Scarlato,G.
TI The 129 codon polymorphism of the prion protein gene influences earlier cognitive performance in Down syndrome subjects
QU Journal of Neurology. Zeitschrift für Neurologie 2003 Jun; 250(6): 688-92
PT journal article
AB Recently, a frequent prion protein gene (PRNP) polymorphism consisting of a methionine (M) for valine (V) substitution at codon 129 has been associated with cognitive impairment in elderly individuals. Down syndrome (DS) is associated with mental retardation and development of Alzheimer-like brain abnormalities. In the present study, we investigated the role of the PRNP polymorphism in 122 relatively young Italian DS patients. Allele frequencies of DS subjects did not differ from those in the general population. However, we found a significantly faster rate of decline in intellectual ability in the subgroup of DS patients carrying at least one V allele compared with the M/M DS subjects. An additive deleterious effect of apolipoprotein E epsilon 4 allele was detected after stratifying by APOE gene status. Our findings provide evidence that variability of the PRNP gene at codon 129 might contribute to accelerating the rate of earlier cognitive decline in DS subjects.
IN Anscheinend nehmen bei Patienten mit dem Down-Syndrom die geistigen Fähigkeiten schneller ab, wenn sie wenigstens ein Allel des Prionproteins mit Valin an Position 129 besitzen.
MH Adolescent; Adult; Age Factors; Alleles; Amino Acid Substitution; Apolipoproteins E/classification/metabolism; Child; Child, Preschool; Codon; Cognition Disorders/etiology/*genetics; Comparative Study; Down Syndrome/*genetics/physiopathology; Female; Follow-Up Studies; Gene Frequency; Genotype; Human; Intelligence Tests; Male; Methionine/genetics; Mutation; *Polymorphism (Genetics); Prions/*genetics; Support, Non-U.S. Gov't; Valine/genetics
AD Dipartimento di Scienze Neurologiche, Padiglione Ponti, I. R. C. S. S. Ospedale Maggiore Policlinico, Via F. Sforza, 35, 20122 Milan, Italy. gpcomi@mailserver.unimi.it
SP englisch
PO Deutschland