title: Autosomal recessive parkinsonism linked to parkin gene in a Tunisian family. Clinical, genetic and pathological study.
abstract: OBJECTIVE
  To report clinical, pathological and genetic findings in a Tunisian kindred with autosomal recessive juvenile parkinsonism (AR-JP) linked to parkin gene.
  
  
  BACKGROUND
  AR-JP has been mapped to chromosome 6q and is caused by several mutations of the parkin gene (Park 2). Pathological features in AR-JP are characterized by neuronal loss in substantia nigra (SN) without Lewy bodies (LB).
  
  
  METHODS
  Three affected siblings with juvenile Parkinson's disease were studied. Pathological examination of the brain was performed in one of them. Linkage studies and mutation analysis of the parkin gene were performed.
  
  
  RESULTS
  Clinical picture was characterized by the association of rest tremor, bradykinesia and rigidity. Parkinsonian signs markedly improved with levodopa treatment in the three siblings. Dystonia was observed in one patient and diurnal fluctuations of parkinsonian signs in another one. Linkage analysis showed homozygous haplotypes in patients as compared to unaffected individuals and mutation analysis of the parkin gene revealed a homozygous two-base AG deletion in exon 2 (101-102). Pathological examination of the brain in one patient showed marked loss of pigmented neurons with extraneuronal free melanin in the lateral and medial parts of the SN associated to a slight spongiosis and astrocytic gliosis. In the locus coeruleus, there was also loss of pigmented neurons without gliosis. No LB or neurofibrillary tangles were found neither by traditional nor by histo-immunological stainings.
  
  
  CONCLUSIONS
  This Tunisian kindred with AR-JP linked to a micro-deletion of the parkin gene shows clinical similarities with the previously reported Japanese and European families. Pathological features of this kindred are compared to what has been reported in AR-JP families linked to large exonic deletions of this gene.
authors.affiliation: Service de Neurologie, Institut National de Neurologie, La Rabta, Tunis 1007, Tunisia. neziha.khouja@rns.tn
authors.forename: Neziha
authors.initials: N
authors.lastname: Gouider-Khouja
authors.forename: Abdelmajid
authors.initials: A
authors.lastname: Larnaout
authors.forename: Rim
authors.initials: R
authors.lastname: Amouri
authors.forename: Sana
authors.initials: S
authors.lastname: Sfar
authors.forename: Samir
authors.initials: S
authors.lastname: Belal
authors.forename: Christiane
authors.initials: C
authors.lastname: Ben Hamida
authors.forename: Mongi
authors.initials: M
authors.lastname: Ben Hamida
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Fayçal
authors.initials: F
authors.lastname: Hentati
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D005192:Family Health; D005260:Female; D006239:Haplotypes; D006801:Humans; D008025:Ligases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000473:pathology*; D010375:Pedigree; D014416:Tunisia; D044767:Ubiquitin-Protein Ligases
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D008025:Ligases