Presymptomatic and early detection in Huntington's disease

Klawans, Harold L.; Goetz, Christopher G.; Perlik, Stuart

doi:10.1002/ana.410080402

Cited by 35 publications

(15 citation statements)

References 33 publications

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“…The degeneration of dopaminergic neurons within the mesDA system is the direct cause of Parkinson disease (7)(8)(9)(10), and other extrapyramidal motor disorders like tardive dyskinesia (36)(37)(38) are also associated with this system. Furthermore, the mesDA system has been implicated in affective disorders like manic depression and schizophrenia (6,39) and in behavioral reinforcement and drug addiction (40).…”

Section: Resultsmentioning

confidence: 99%

A homeodomain gene Ptx 3 has highly restricted brain expression in mesencephalic dopaminergic neurons

Smidt

Schaick

Lanctôt

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

337

275

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The mesencephalic dopaminergic (mesDA) system regulates behavior and movement control and has been implicated in psychiatric and affective disorders. We have identified a bicoid-related homeobox gene, Ptx3, a member of the Ptx-subfamily, that is uniquely expressed in these neurons. Its expression starting at E11.5 in the developing mouse midbrain correlates with the appearance of mesDA neurons. The number of Ptx3-expressing neurons is reduced in Parkinson patients, and these neurons are absent from 6-hydroxydopamine-lesioned rats, an animal model for this disease. Thus, Ptx3 is a unique transcription factor marking the mesDA neurons at the exclusion of other dopaminergic neurons, and it may be involved in developmental determination of this neuronal lineage.The patterning of the developing mammalian brain is thought to involve cascades of signaling molecules and transcription factors, but the mechanisms for generation of distinct neuronal cell types during terminal differentiation are still largely speculative (1, 2). Yet, the specification of individual neuronal phenotypes underlies the assembly of neural circuits essential for brain function. The mesencephalic dopaminergic (mesDA) system consists of a limited set of neurons that are well defined anatomically and functionally (3-5). Their specific degeneration in Parkinson disease reveals their functional properties in control of behavior and movement as well as a unique vulnerability (6-10). In a search for homeobox genes associated with a unique neuronal lineage, we isolated a cDNA encoding a bicoid-related homeobox gene Ptx3, a member of the Ptx subfamily (11)(12)(13)(14). This gene is strictly expressed in mesDA neurons. METHODS AND MATERIALSCloning of Ptx3 Gene Transcripts. Poly(A) ϩ RNA from hypothalamic fragments of the adult rat brain were subjected to reverse transcriptase-PCR with primers based on brainexpressed homeobox genes: upstream, 5Ј-GMRSCGM-SAVMGSACMMBCTTYAC-3Ј; downstream, 5Ј-TGGT-TYMRVAAYCGYHGMGCMARRTG-3Ј. The annealing temperature was 40°C. The PCR product was used to screen an adult rat hypothalamus library in gt11. Isolated phage DNA was cut with EcoRI, the insert of Ϸ1.2 kb was subcloned into pGEM7Zf(ϩ), and both strands of the insert were sequenced.Northern Analysis. Total RNA extracted from tissues of the adult rat by Rnazol (Biotecx Laboratories, Houston) was fractionated on formaldehyde-agarose gels and transferred onto a nylon membrane (Hybond-N, Amersham) by downward capillary blotting. Blots were hybridized with a 32 P-randomprimed-labeled complete Ptx3 cDNA at 65°C overnight (15). Autoradiography was performed with a Fujix BAS1000 phosphor-imager (Fuji).Cell Culture, Transfection, and Gel Retardation Assays. Murine fibroblast L cells were grown in DMEM supplemented with 10% FCS. L cells were transfected by the calcium phosphate method (16). Precipitate containing 3 g of reporter plasmid, 1 g of effector plasmid, 1 g of RSV-human growth hormone (hGH) internal control plasmid, and 5 g of carrier DNA (pSP64, Promega) was app...

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Section: Resultsmentioning

confidence: 99%

A homeodomain gene Ptx 3 has highly restricted brain expression in mesencephalic dopaminergic neurons

Smidt

Schaick

Lanctôt

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

337

275

View full text Add to dashboard Cite

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“…Each patient was tested twice in each modality to replicate results. Silver chloride or gold-plated electrodes, secured to the scalp with electrode · paste, were placed at F., C., and P, (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) International Electrode System), and all were referenced to the right ear-A,. All of the electrode impedences were less than 5 kf!…”

Section: Event-related Potentialsmentioning

confidence: 99%

Cognitive Evoked Potentials (P300) in Early Huntington's Disease

Rosenberg¹,

Nudleman²,

Starr³

1985

Archives of Neurology

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“…The search for a reliable predictive test for gene carriers of HD has received considerable attention [Klawans et al, 1980;Propert, 19801 and produced much controversy [Emery, 19801. Although no such test is now available, the recent identification of a DNA restriction fragment length polymorphism closely linked to the HD gene [Gusella et al, 19831 may soon provide the capability to identify gene carriers before the onset of symptoms [Housman and Gusella, 19821.…”

Section: Introductionmentioning

confidence: 99%

Potential impact of a predictive test on the gene frequency of Huntington disease

et al. 1984

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Fifty-five individuals at 50% risk of inheriting Huntington disease (HD) were given in-depth structured interviews to survey attitudes toward use of a predictive test and to assess the possible impact of such a test on the number of gene carriers born. Three-quarters of the sample said they would take predictive test. Given a positive predictive or prenatal test, the number of individuals choosing to have children is reduced from 80% of the total sample to 42%, or by almost one-half. The large proportion of at risk individuals who say they would use a predictive test underscores the importance of developing guidelines for its administration prior to implementation.

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Presymptomatic and early detection in Huntington's disease

Abstract: This review summarizes research techniques that have been applied to the early diagnosis and presymptomatic detection of Huntington's disease. Presently, no one test definitively discriminates between nonaffected persons and carriers.

Cited by 35 publications

References 33 publications

A homeodomain gene Ptx 3 has highly restricted brain expression in mesencephalic dopaminergic neurons

A homeodomain gene Ptx 3 has highly restricted brain expression in mesencephalic dopaminergic neurons

Cognitive Evoked Potentials (P300) in Early Huntington's Disease

Potential impact of a predictive test on the gene frequency of Huntington disease

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