Genetic linkage studies in autosomal dominant parkinsonism: Evaluation of seven candidate genes

T. Gasser, Z. K. Wszolek, J. Trofatter, L. Ozelius, R. J. Uitti, C. S. Lee, J. Gusella, Ronald Pfeiffer, D. B. Calne, X. O. Breakefield

Research output: Contribution to journalArticle

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Abstract

Linkage studies were performed in three families (A, B, and C) with autosomal dominantly inherited parkinsonism affecting multiple members in three generations. Affected individuals exhibited the cardinal signs and symptoms of Parkinson's disease, with a mean age of onset of 51, 62, and 61 years in Families A, B, and C, respectively. Parkinsonian symptoms responded to L-dopa treatment, and an [18F]6-fluoro-L-dopa positron emission tomography scan in 1 affected member of Family B showed decreased striatal uptake typical of Parkinson's disease. Ancestors of all three families were traced to a small region in northern Germany and southern Denmark, suggesting the possibility of a common mutation. Linkage studies were performed with polymorphic markers associated with the following candidate genes: the genes for glutathione peroxidase (GPX1, 3q11), tyrosine hydroxylase (TH, 11p15.5), brain-derived neurotrophic factor (BDNF, 11p14), catalase (CAT, 11p13), amyloid precursor protein (APP, 21q21), copper-zinc superoxide dismutase (SOD1, 21q21), and debrisoquin 4-hydroxylase (CYP2D6, 22q13.1). Summed lod scores for all families excluded linkage to the genes GPX1, TH, APP, SOD1, and CYP2D6, as well as to the chromosomal region containing the genes CAT and BDNF. If families were analyzed individually, exclusion was possible for two (Family A), six (Family B), and five (Family C) of the seven candidate genes. There was strong evidence against linkage for the remaining loci in all families analyzed individually, except for TH, which was uninformative in Families A and B, and CYP2D6, which gave slightly positive pairwise lod scores in Family A. Our results indicate that the candidate genes investigated are not involved in the etiology of parkinsonism in these families.

Original languageEnglish (US)
Pages (from-to)387-396
Number of pages10
JournalAnnals of Neurology
Volume36
Issue number3
StatePublished - Sep 1994
Externally publishedYes

Fingerprint

Genetic Linkage
Parkinsonian Disorders
Genes
Cytochrome P-450 CYP2D6
Brain-Derived Neurotrophic Factor
Lod Score
Levodopa
Parkinson Disease
Debrisoquin
Corpus Striatum
Amyloid beta-Protein Precursor
Tyrosine 3-Monooxygenase
Denmark
Mixed Function Oxygenases
Age of Onset
Positron-Emission Tomography
Catalase
Superoxide Dismutase
Signs and Symptoms
Germany

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Gasser, T., Wszolek, Z. K., Trofatter, J., Ozelius, L., Uitti, R. J., Lee, C. S., ... Breakefield, X. O. (1994). Genetic linkage studies in autosomal dominant parkinsonism: Evaluation of seven candidate genes. Annals of Neurology, 36(3), 387-396.

Genetic linkage studies in autosomal dominant parkinsonism : Evaluation of seven candidate genes. / Gasser, T.; Wszolek, Z. K.; Trofatter, J.; Ozelius, L.; Uitti, R. J.; Lee, C. S.; Gusella, J.; Pfeiffer, Ronald; Calne, D. B.; Breakefield, X. O.

In: Annals of Neurology, Vol. 36, No. 3, 09.1994, p. 387-396.

Research output: Contribution to journalArticle

Gasser, T, Wszolek, ZK, Trofatter, J, Ozelius, L, Uitti, RJ, Lee, CS, Gusella, J, Pfeiffer, R, Calne, DB & Breakefield, XO 1994, 'Genetic linkage studies in autosomal dominant parkinsonism: Evaluation of seven candidate genes', Annals of Neurology, vol. 36, no. 3, pp. 387-396.
Gasser T, Wszolek ZK, Trofatter J, Ozelius L, Uitti RJ, Lee CS et al. Genetic linkage studies in autosomal dominant parkinsonism: Evaluation of seven candidate genes. Annals of Neurology. 1994 Sep;36(3):387-396.
Gasser, T. ; Wszolek, Z. K. ; Trofatter, J. ; Ozelius, L. ; Uitti, R. J. ; Lee, C. S. ; Gusella, J. ; Pfeiffer, Ronald ; Calne, D. B. ; Breakefield, X. O. / Genetic linkage studies in autosomal dominant parkinsonism : Evaluation of seven candidate genes. In: Annals of Neurology. 1994 ; Vol. 36, No. 3. pp. 387-396.
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AU - Lee, C. S.

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