title: Phenotypic variability of PINK1 expression: 12 Years' clinical follow-up of two Italian families.
abstract: BACKGROUND
  Mutations in the PINK1 gene are the second most frequent cause of autosomal recessive early-onset parkinsonism.
  
  
  METHODS
  We evaluated five affected PINK1 homozygous and 14 heterozygous mutation carriers from two large Italian families over a 12-year follow-up period. Motor, nonmotor, cognitive, psychiatric, and behavioral profiles were systematically assessed. Four homozygotes and eight heterozygotes underwent magnetic resonance imaging.
  
  
  RESULTS
  All homozygotes showed a mild progression of motor signs and a persistent excellent response to levodopa. All but one patient complained of nonmotor symptoms and sleep impairment. Three presented impulse control disorders and two anxiety and apathy. All obtained abnormal scores at Montreal Cognitive Assessment (MoCA) and in tests sensitive to frontal functions; one presented a global cognitive impairment. Three heterozygotes showed motor signs and were diagnosed as possibly affected. They had nonmotor symptoms and cognitive impairment, and two of them showed mild bilateral temporal atrophy. Five unaffected heterozygotes reported abnormal scores at MoCA and low performances at tests sensitive to frontal functions.
  
  
  CONCLUSIONS
  We expanded the phenotypic profile of PINK1-related parkinsonism, including psychiatric and cognitive features as part of clinical presentation.
authors.affiliation: Institute of Neurology, Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Ricciardi
authors.forename: Simona
authors.initials: S
authors.lastname: Petrucci
authors.forename: Arianna
authors.initials: A
authors.lastname: Guidubaldi
authors.forename: Tamara
authors.initials: T
authors.lastname: Ialongo
authors.forename: Laura
authors.initials: L
authors.lastname: Serra
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ferraris
authors.forename: Barbara
authors.initials: B
authors.lastname: Spanò
authors.forename: Marco
authors.initials: M
authors.lastname: Bozzali
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Bentivoglio
mesh_terms: D000328:Adult; D018450:Disease Progression; D017407:Family Leave; D005260:Female; D006579:Heterozygote; D006801:Humans; D007558:Italy; D008137:Longitudinal Studies; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020734:Parkinsonian Disorders / Q000235:genetics*; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics*; D012720:Severity of Illness Index; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase
keywords: PINK1; Parkinson disease; autosomal recessive early-onset parkinsonism; heterozygotes; nonmotor signs