title: Three parkin gene mutations in a sibship with autosomal recessive early onset parkinsonism.
abstract: The objective was to describe a family with autosomal recessive, early onset parkinsonism, with affected siblings carrying three different exon rearrangements in the parkin gene. The living affected siblings were personally examined. Molecular genetic analyses included exon dosage of the parkin gene using a semiquantitative multiplex polymerase chain reaction (PCR) protocol and haplotype analysis. The index case was a compound heterozygote with a deletion of exon 5 and a duplication of exon 3. His affected sister was a compound heterozygote for a deletion of exon 5 and a deletion of exons 3-9. Haplotype analysis confirmed the presence of three mutant alleles at the parkin locus. The phenotype was early onset parkinsonism with marked response to levodopa, and a very slow, prolonged course. In conclusion, the frequency of mutations in the parkin gene in certain populations might be high enough to cause allelic heterogeneity in the same sibship.
authors.affiliation: Department of Neurological Sciences, La Sapienza, University, Rome, Italy. bonifati@kgen.fgg.eur.nl
authors.forename: V
authors.initials: V
authors.lastname: Bonifati
authors.forename: C B
authors.initials: CB
authors.lastname: Lücking
authors.forename: E
authors.initials: E
authors.lastname: Fabrizio
authors.forename: M
authors.initials: M
authors.lastname: Periquet
authors.forename: G
authors.initials: G
authors.lastname: Meco
authors.forename: A
authors.initials: A
authors.lastname: Brice
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002872:Chromosome Deletion; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006580:Genetic Carrier Screening; D006801:Humans; D008025:Ligases / Q000235:genetics*; D008297:Male; D009460:Neurologic Examination; D020734:Parkinsonian Disorders / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D044767:Ubiquitin-Protein Ligases
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases