Localization of a novel locus for autosomal recessive early-onset parkinsonism, PARK6, on human chromosome 1p35-p36

Anna Rita Bentivoglio, Alberto Albanese, Tamara Ialongo, Enza Maria Valente, Ph Dixon, Alessandro Ferraris, Marina Frontali, Nw Wood

Risultato della ricerca: Contributo in rivistaArticolo in rivista

360 Citazioni (Scopus)

Abstract

The cause of Parkinson disease (PD) is still unknown, but genetic factors have recently been implicated in the etiology of the disease. So far, four loci responsible for autosomal dominant PD have been identified. Autosomal recessive juvenile parkinsonism (ARJP) is a clinically and genetically distinct entity; typical PD features are associated with early onset, sustained response to levodopa, and early occurrence of levodopa-induced dyskinesias, which are often severe. To date, only one ARJP gene, Parkin, has been identified, and multiple mutations have been detected both in families with autosomal recessive parkinsonism and in sporadic cases. The Parkin-associated phenotype is broad, and some cases are indistinguishable from idiopathic PD. In > or = 50% of families with ARJP that have been analyzed, no mutations could be detected in the Parkin gene. We identified a large Sicilian family with four definitely affected members (the Marsala kindred). The phenotype was characterized by early-onset (range 32-48 years) parkinsonism, with slow progression and sustained response to levodopa. Linkage of the disease to the Parkin gene was excluded. A genomewide homozygosity screen was performed in the family. Linkage analysis and haplotype construction allowed identification of a single region of homozygosity shared by all the affected members, spanning 12.5 cM on the short arm of chromosome 1. This region contains a novel locus for autosomal recessive early-onset parkinsonism, PARK6. A maximum LOD score 4.01 at recombination fraction .00 was obtained for marker D1S199.
Lingua originaleEnglish
pagine (da-a)895-900
Numero di pagine6
RivistaAmerican Journal of Human Genetics
Volume68
Stato di pubblicazionePubblicato - 2001

Keywords

  • Adult
  • Age of Onset
  • Chromosome Mapping
  • Chromosomes, Human, Pair 1
  • Female
  • Genes, Recessive
  • Genetic Heterogeneity
  • Genetic Linkage
  • Genetic Markers
  • Haplotypes
  • Homozygote
  • Humans
  • Italy
  • Ligases
  • Lod Score
  • Male
  • Middle Aged
  • Parkinsonian Disorders
  • Pedigree
  • Phenotype
  • Proteins
  • Ubiquitin-Protein Ligases

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