title: A novel Cys212Tyr founder mutation in parkin and allelic heterogeneity of juvenile Parkinsonism in a population from North West Colombia.
abstract: We report the molecular characterization of three multiplex families and a sporadic case of juvenile Parkinsonism identified in the province of Antioquia (Colombia). Linkage and haplotype analysis using markers in 6q25.2-27 indicated that Parkinsonism in the pedigrees is linked to the parkin gene (maximum LOD-score of 3.85) but that they carry two different mutant haplotypes. Sequence analysis revealed a novel G to A transition in exon 6 at position 736 (G736A) of parkin. This change results in a non-conservative cysteine for tyrosine substitution. All affected individuals from two families were homozygous for this mutation, which was not detected in 100 normal controls. Patients from the family carrying the second haplotype and the sporadic case were homozygous for a GT insertion in exon 3. This mutation has been previously identified in French families with juvenile Parkinsonism. The concomitant presence of founder effects and allelic heterogeneity in Antioquia might relate to the founding admixture at the origin of this population.
authors.affiliation: Laboratorio de Genética Molecular, Facultad de Medicina, Universidad de Antioquia, A.A. 1226 Medellín, Colombia.
authors.forename: N
authors.initials: N
authors.lastname: Pineda-Trujillo
authors.forename: L G
authors.initials: LG
authors.lastname: Carvajal-Carmona
authors.forename: O
authors.initials: O
authors.lastname: Buriticá
authors.forename: S
authors.initials: S
authors.lastname: Moreno
authors.forename: C
authors.initials: C
authors.lastname: Uribe
authors.forename: D
authors.initials: D
authors.lastname: Pineda
authors.forename: M
authors.initials: M
authors.lastname: Toro
authors.forename: F
authors.initials: F
authors.lastname: García
authors.forename: W
authors.initials: W
authors.lastname: Arias
authors.forename: G
authors.initials: G
authors.lastname: Bedoya
authors.forename: F
authors.initials: F
authors.lastname: Lopera
authors.forename: A
authors.initials: A
authors.lastname: Ruiz-Linares
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D003105:Colombia; D003545:Cysteine / Q000235:genetics; D005192:Family Health; D005260:Female; D018703:Founder Effect; D018740:Genetic Heterogeneity; D006801:Humans; D008025:Ligases / Q000235:genetics*; D008297:Male; D020734:Parkinsonian Disorders / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D014443:Tyrosine / Q000235:genetics; D044767:Ubiquitin-Protein Ligases
chemical_list: D014443:Tyrosine; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D003545:Cysteine