Re: Fwd: [Fwd: Research letters : Codon 129 prion protein genotype and...

[Guest guest]

DBC006@... wrote:

>

> Terry:

>

> I can't find a link for this... can you supply one... or a website

> address?

>

> Thanks...

>

> Dolly

>

> ---------------------------------------------------------------

>

> Subject: [Fwd: Research letters : Codon 129 prion protein genotype

> and sporadic Creutzfeldt-Jakob disease]

> Date: Fri, 14 May 1999 07:57:45 -0500

>

> Reply-To: cjdvoice (AT) onelist (DOT) com

> Organization: MADSON

> To: cjdvoice (AT) onelist (DOT) com

>

> -- Liz and , Good Morning,

> 1st (I hope you can read this, if not, I will post on board),

> 2nd Recently, we have spoken about Florid Plaque and or kuru plaque, and

> the fact that both Liz Father and Husband had them, and the fact

> of the age of Husband, (41). This article that came out of the

> Lancet this week states (second to last paragraph), IT IS OF NOTE THAT

> WIDESPREAD FLORID PLAQUE DEPOSTITION, WHICH IS THE NEUROPATHOLOGICAL

> HALLMARK OF VARIANT CJD.....

> thought you might be interested in this........

> I think both of these cases could be questionable, for v-CJD???

>

> --------------------

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> Subject: Research letters : Codon 129 prion protein genotype and sporadic

> Creutzfeldt-Jakob disease

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> Research letters : Codon 129 prion protein genotype an=

> d sporadic Creutzfeldt-Jakob disease

>

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> an=3D2 align=3Dcenter bgcolor=3D99ccff> er=3D0> 15 width=3D157 alt=3D " Research letters " align=3Dtop> t border=3D0>Volume 353, Number 9165 ancet/images/site/gen/spacer.gif " border=3D0 height=3D1 width=3D20 align=3D=

> top> 15 May 1999

> arly1662.html " target=3D " body " > rev.gif " border=3D0 height=3D10 width=3D49 alt=3D " Previous " align=3D " top " =

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> 30 alt=3D " Next " align=3D " top " vspace=3D4 hspace=3D4>

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> ldtjakobdisease " >

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> Codon 129 pri=

> on protein genotype and sporadic Creutzfeldt-Jakob disease

>

>

> e/gen/dot_blue.gif " border=3D0 height=3D1 width=3D13 align=3Dtop>

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>

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>

> A Alperovitch, I Zerr, M Pocchiari, E Mitrova, J de Pedro Cuesta, I He=

> gyi, S , H Kretzschmar, C van Duijn, RG Will

>

>

> Methionine homozygosity at codon 129 of the prion protein (PrP) gene is a=

> recognised risk factor for the development of sporadic Creutzfeldt-Jakob=

> disease (CJD).1 Between 64 and 81% of sporadic cases have thi=

> s genotype,1-3 with an overall rate, combining the data from t=

> hree series, of 71%. PrP gene analysis is now available in 748 out of 132=

> 7 cases of definite or probable sporadic CJD, including data from Austral=

> ia (5), France (217), Germany (239), Italy (101), the Netherlands (36), S=

> lovakia (7), Spain (7), Switzerland (7), and the UK (129). A current issu=

> e is whether cases of variant CJD (nvCJD), might occur in individuals wit=

> h a valine homozygous or heterozygous PrP genotype. To date, all 36 cases=

> of variant CJD with available genetic analysis have been methionine homo=

> zygotes and died at an early age (mean 29 years). A small number of cases=

> of sporadic CJD with a relatively early age at death have been identifie=

> d in participating countries including Australia, France, Germany, the Ne=

> therlands, and the UK. We analysed the distribution of genotypes at codon=

> 129 of the PrP gene by 10-year age groups in order to determine whether =

> there is a relative excess of young valine homozygote or heterozygote cas=

> es of sporadic CJD.

>

>

>

>

> MM MV VV</=

> TD>

> <49 years* 43 (23) 17 (9) 41 (22)</=

> TD>

> 50-59 years 65 (97) 16 (24) 19 (28)

D>

> 60-69 years 75 (227) 13 (40) 12 (36)</=

> TD>

> 70-79 years 73 (148) 10 (21) 17 (35)</=

> TD>

> 80+ years 84 (32) 11 (4) 5 (2) <=

> /TR>

> Total 70 (527) 13 (98) 16 (123) <=

> /TR>

> Previous studiesÝ 71 (60) 17 (14) <=

> TD>12 (10)

> European data 74 (252) 11 (38) 15 (51)=

>

> 1993-95

> European data 68 (275) 15 (60) 18 (72)=

>

> 1996-98

> Normal population 39 (156) 50 (198) 11=

> (44)

> *The age of death of the youngest case for each genot=

> ype was 28 years for MM, 20 years for MV, and 23 years for VV. ÝLa=

> planche J-L, et al. Molecular genetics of prion diseases in France. Ne=

> urology 1994; 44: 2347-51, and Salvatore M, et al. Polymorphis=

> ms of the prion protein gene in Italian patients with Creutzfeldt-Jakob d=

> isease. Hum Genet 1995; 94: 375-79.

> Percentage of codon 129 PRP genotypes in sporadic =

> CJD by 10-year age groups in the European study 1993-1998 (numbers of cas=

> es in parentheses), and codon 129 distribution in the normal population a=

> nd in previous studies of sporadic CJD

>

>

>

> The table shows data on the distribution of PrP genotypes in the normal w=

> hite population, pooling data from five studies4 (there are no=

> data on stratification by age in these studies), and the genotype distri=

> bution in sporadic CJD, derived by pooling data from three studies (table=

> 2), are also shown, together with previous data from the Europ=

> ean surveillance project.3 The frequencies of codon 129 PrP ge=

> notypes differ significantly across the age groups ( t/images/characters/nR-chi.gif " border=3D0 height=3D20 width=3D9 alt=3D " (=

> chi) " align=3D " middle " >2=3D38·2, 8 df, p<0·0001) =

> and there is a positive linear relation between age and the frequency of =

> the methionine homozygote genotype (p for linear trend <0·0001). =

> The valine homozygous genotype is significantly more frequent in cases ag=

> ed 49 years or less compared with those aged 50 years and over ( " /newlancet/images/characters/nR-chi.gif " border=3D0 height=3D20 width=3D=

> 9 alt=3D " (chi) " align=3D " middle " >2=3D27·9, 2 df, p<0=

> 183;0001). In some countries only limited data are available but comparis=

> ons between countries are possible for France, Germany, Italy, and the UK=

> =2E Codon 129 distribution in these countries is not significantly differ=

> ent from previous studies of sporadic CJD, and within country comparison =

> of cases aged less than 50 years shows a significant excess of valine hom=

> ozygotes in France, Germany, and the UK, but not in Italy. There is a non=

> -significant excess of heterozygote cases aged less than 50 years in Ital=

> y, the Netherlands, and the UK.

>

>

> The relative excess of valine homozygotes in sporadic CJD aged less than =

> 50 years is unexpected. There are a number of possible reasons. There may=

> be a bias in the surveillance system for the identification of younger a=

> typical cases of sporadic CJD, because of increased interest in younger s=

> uspect cases after the identification of variant CJD. Sporadic CJD with a=

> n atypical clinicopathological phenotype may occur in younger patients, p=

> articularly those with a valine homozygous genotype.4 These ca=

> ses rarely have the " typical " electroencephalogram seen in sporadic CJD a=

> nd might be over-represented in systematic surveillance data because of a=

> scertainment bias. It is also possible that CJD is underdiagnosed in olde=

> r valine homozygotes because of an atypical phenotype, although the genot=

> ype distribution we have identified would necessitate underdiagnosis in t=

> he 50-59 year age group in which alternative causes of dementia are fairl=

> y uncommon. It is also difficult to understand why there should be a diff=

> erential bias in the diagnosis of those aged over 50 years compared with =

> younger cases, when suspect cases are investigated in a standard manner, =

> independent of age, and this often includes 14-3-3 cerebrospinal fluid im=

> munoassay and necropsy examination. The percentages of heterozygote and v=

> aline homozygote cases between the study periods 1993-95 and 1996-98 are =

> not statistically different, and this finding does not support the hypoth=

> esis of an increase in the ascertainment of younger heterozygote or valin=

> e homozygote cases with time as a result of the identification of variant=

> CJD in March, 1996.

>

>

> It is possible that the excess of valine homozygotes in younger cases is =

> caused by variation in the strain of infectious agent and perhaps exogeno=

> us infection, either iatrogenic or zoonotic, for example due to bovine sp=

> ongiform encephalopathy (BSE). An excess of valine homozygotes has been f=

> ound in growth-hormone recipients with CJD,5 but none of the c=

> ases in our report were known to have an iatrogenic exposure. The possibi=

> lity that the excess of young valine homozygote cases reflects disease ca=

> used by BSE is unlikely because there is no differential excess of valine=

> homozygote cases in the UK, the country with the greatest potential huma=

> n exposure to BSE, compared with France and Germany. Furthermore all case=

> s of variant CJD tested to date in the UK have been methionine homozygote=

> s and it would be surprising if cases of variant CJD with this genotype w=

> ere not identified at the same time, and probably earlier, than valine ho=

> mozygote BSE-related cases in other countries, should such cases actually=

> occur. One methionine homozygote French case of variant CJD has been ide=

> ntified. It is of note that widespread florid plaque deposition, which is=

> the neuropathological hallmark of variant CJD, has not been found in any=

> of the valine homozygote cases in this series. Most of these cases have =

> undergone necropsy and PrP glycoform analysis in a small number of cases,=

> including three young valine homozygote cases in the UK, has not shown t=

> he PrP subtype identified in variant CJD nor the type 5 subtype found in =

> BSE transmissions to laboratory mice expressing valine at codon 129. Furt=

> her analysis of temporal trends in codon 129 genotype distribution, clini=

> copathological features, and prion protein glycoform patterns in younger =

> patients with CJD is being undertaken.

>

>

> The data in this paper have been accumulated by many people in each parti=

> cipating country. J Ironside and M Head provided the data of PrP glycofor=

> m analysis in the UK. The study is funded by the European Union, contract=

> number BMH4-CT97-2216.

>

>

> 1 Palmer MS, Dryden AJ, JT, Collinge J. Homozygous prion prot=

> ein genotype predisposes to sporadic Creutzfeldt-Jakob disease. Nature=

> 1991; 352: 340-41.

>

>

> 2 Lampe J, Kitzler H, Walter MC, Lochmuller H, Reichmann H. Methioni=

> ne homozygosity at prion protein gene codon 129 may predispose to sporadi=

> c inclusion-body myositis. Lancet 1999; 353: 465-66.

>

>

> 3 Will RG, Alperovitch A, Poser S, et al. Descriptive epidemiology o=

> f Creutzfeldt-Jakob disease in six European countries, 1993-1995. Ann=

> Neurol 1998; 43: 763-67.

>

>

> 4 Parchi P, Castellani R, Capellari S, et al. Molecular basis of phe=

> notypic variability in sporadic Creutzfeldt-Jakob disease. Ann Neurol =

> 1996; 39: 767-78.

>

>

> 5 Collinge J, Palmer MS, Dryden AJ. Genetic predisposition to iatrog=

> enic Creutzfeldt-Jakob disease. Lancet 1991; 337: 1441-442=

> =2E

>

>

> INSERM U.360, Hôpital La Salpêtrière 75651, Paris, =

> cedex 13, France; Department of Neurology and Neuropathology, University =

> of Göttingen, Göttingen, Germany; Istituto Superiore di Sanit&a=

> grave;, Laboratory of Virology, 00161 Rome, Italy; Institute of Preventiv=

> e and Clinical Medicine, National Reference Centre of Slov Virus Neuroinf=

> ections, 833 01 Bratislava, Slovakia; Instituto de Salud III, Cent=

> ro Nacional de Epidemiologia, Departmento de Epidemiologia Aplicada, Madr=

> id, Spain; UniversitätsSpital Zürich, Institut für Neuropa=

> thologie, CH-8091 Zürich, Switzerland; Department of Pathology, The =

> University of Melbourne, Vic 3052, Australia; Department of Epidemiology =

> & Biostatistics, Erasmus University Medical School, PO Box 1738, Rott=

> erdam, Netherlands; The National CJD Surveillance Unit, Western General H=

> ospital, Edinburgh, EH4 2XU, UK (R Will)

>

>

>

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Dolly, it's in this weeks Lancet...........

http://www.thelancet.com/newlancet/reg/issues/vol353no9165/body.research1673.ht\

ml>

I doubt, you will reach it through this address.

I can fax.......

Could you read it???