Parkin-proven disease: Common founders but divergent phenotypes

S. Lincoln, J. Wiley, T. Lynch, J. W. Langston, R. Chen, A. Lang, E. Rogaeva, D. S. Sa, R. P. Munhoz, J. Harris, K. Marder, C. Klein, G. Bisceglio, J. Hussey, A. West, M. Hulihan, J. Hardy, M. Farrer*

*Korrespondierende/r Autor/-in für diese Arbeit
17 Zitate (Scopus)

Abstract

Objective: To compare and contrast clinical and genetic findings in six probands with parkinsonism with a parkin exon 3 438- to 477-bp deletion (Ex3Δ40) to search for evidence of a common founder. Method: Clinical review, parkin gene sequencing, dosage studies, and high-resolution genotype/haplotype analysis were performed. Results: All subjects had two or more signs consistent with a diagnosis of possible or probable PD with age at onset younger than 45 years (mean ± SD 29.3 ± 10.2 years, range 16 to 42 years). Affected individuals were either homozygotes, compound heterozygotes, or Ex3Δ40 carriers with one normal parkin allele. Haplotype analysis revealed both Ex3Δ40 and Ex7 924 C→T (R275W) mutations originated from common founders, the former most probably of Irish descent. Although three cases had Ex7 924 C→T (R275W) and Ex3Δ40 mutations, their clinical presentation and mode of inheritance were variable. Conclusion: Parkin mutations on common parkin haplotypes provide testable hypotheses of parkin function in genetically defined parkinsonism.

OriginalspracheEnglisch
ZeitschriftNeurology
Jahrgang60
Ausgabenummer10
Seiten (von - bis)1605-1610
Seitenumfang6
ISSN0028-3878
DOIs
PublikationsstatusVeröffentlicht - 27.05.2003

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