title: Molecular findings in familial Parkinson disease in Spain.
abstract: BACKGROUND
  Several genetic errors in alpha-synuclein (Park1) and ubiquitin carboxyl-terminal-hydrolase L1(Park5) genes cause autosomal dominant familial Parkinson disease. Mutations in the parkin gene (Park2) are the major cause of autosomal recessive Parkinson disease.
  
  
  OBJECTIVE
  To analyze the clinical and molecular data of 19 Spanish kindreds (13 with recessive, 4 with dominant, and 2 with uncertain inheritance) who have familial Parkinson disease.
  
  
  METHODS
  We searched for the previously described mutations in Park1 and Park5 genes and for new or described mutations in Park2. We used single-strand conformation polymorphism, direct sequencing, and restriction digestion of polymerase chain reaction (PCR)-amplified genomic DNA for this study.
  
  
  RESULTS
  None of these families have either Park1 or Park5 mutations. We found 5 different mutations in Park2 gene in 5 of the families with recessive inheritance. To our knowledge, 2 of these mutations, V56E and C212Y, have not been previously reported. The other mutations found (deletion of exons 3 and 5 and 225delA) have been described in other ethnic groups. Heterozygous carriers of a single Park2 mutation either were asymptomatic or developed clinical symptoms in late adulthood or after brief exposure to haloperidol therapy.
  
  
  CONCLUSIONS
  Mutations in Park2 gene account for 38% of the families with recessive parkinsonism in Spain. We found 2 cases of simple heterozygous Park2 mutation carriers that developed clinical symptoms, either in late adulthood or after brief exposure to parkinsonizing agents. Thus, hereditary Parkinson disease has more variable clinical phenotype and molecular defects than previously thought since heterozygous mutations could be a risk factor for parkinsonism.
authors.affiliation: Banco de Tejidos para Investigaciones Neurológicas, Facultad de Medicina, Universidad Complutense de Madrid, Pabellón III, sótano, Avda Complutense s/n Madrid 28040, Spain. jhoenicka@cbm.uam.es
authors.forename: Janet
authors.initials: J
authors.lastname: Hoenicka
authors.forename: Lídice
authors.initials: L
authors.lastname: Vidal
authors.forename: Blas
authors.initials: B
authors.lastname: Morales
authors.forename: Israel
authors.initials: I
authors.lastname: Ampuero
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Jiménez-Jiménez
authors.forename: Jose
authors.initials: J
authors.lastname: Berciano
authors.forename: Teodoro
authors.initials: T
authors.lastname: del Ser
authors.forename: Adriano
authors.initials: A
authors.lastname: Jiménez
authors.forename: Pedro G
authors.initials: PG
authors.lastname: Ruíz
authors.forename: Justo G
authors.initials: JG
authors.lastname: de Yébenes
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D015139:Blotting, Southern; D004252:DNA Mutational Analysis; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020734:Parkinsonian Disorders / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D013030:Spain; D051843:Synucleins; D013869:Thiolester Hydrolases / Q000235:genetics; D043222:Ubiquitin Thiolesterase; D051844:alpha-Synuclein
chemical_list: D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase