PMID- 10072423
OWN - NLM
STAT- MEDLINE
DCOM- 19990429
LR  - 20190513
IS  - 0964-6906 (Print)
IS  - 0964-6906 (Linking)
VI  - 8
IP  - 4
DP  - 1999 Apr
TI  - A wide variety of mutations in the parkin gene are responsible for autosomal
      recessive parkinsonism in Europe. French Parkinson's Disease Genetics Study Group
      and the European Consortium on Genetic Susceptibility in Parkinson's Disease.
PG  - 567-74
AB  - Autosomal recessive juvenile parkinsonism (AR-JP, PARK2; OMIM 602544), one of the
      monogenic forms of Parkinson's disease (PD), was initially described in Japan. It
      is characterized by early onset (before age 40), marked response to levodopa
      treatment and levodopa-induced dyskinesias. The gene responsible for AR-JP was
      recently identified and designated parkin. We have analysed the 12 coding exons
      of the parkin gene in 35 mostly European families with early onset autosomal
      recessive parkinsonism. In one family, a homozygous deletion of exon 4 could be
      demonstrated. By direct sequencing of the exons in the index patients of the
      remaining 34 families, eight previously undescribed point mutations (homozygous
      or heterozygous) were detected in eight families that included 20 patients. The
      mutations segregated with the disease in the families and were not detected on
      110-166 control chromosomes. Four mutations caused truncation of the parkin
      protein. Three were frameshifts (202-203delAG, 255delA and 321-322insGT) and one 
      a nonsense mutation (Trp453Stop). The other four were missense mutations
      (Lys161Asn, Arg256Cys, Arg275Trp and Thr415Asn) that probably affect amino acids 
      that are important for the function of the parkin protein, since they result in
      the same phenotype as truncating mutations or homozygous exon deletions. Mean age
      at onset was 38 +/- 12 years, but onset up to age 58 was observed. Mutations in
      the parkin gene are therefore not invariably associated with early onset
      parkinsonism. In many patients, the phenotype is indistinguishable from that of
      idiopathic PD. This study has shown that a wide variety of different mutations in
      the parkin gene are a common cause of autosomal recessive parkinsonism in Europe 
      and that different types of point mutations seem to be more frequently
      responsible for the disease phenotype than are deletions.
FAU - Abbas, N
AU  - Abbas N
AD  - INSERM U289, Hopital de la Salpetriere, 47 Boulevard de l'Hopital, 75651 Paris
      Cedex 13, France.
FAU - Lucking, C B
AU  - Lucking CB
FAU - Ricard, S
AU  - Ricard S
FAU - Durr, A
AU  - Durr A
FAU - Bonifati, V
AU  - Bonifati V
FAU - De Michele, G
AU  - De Michele G
FAU - Bouley, S
AU  - Bouley S
FAU - Vaughan, J R
AU  - Vaughan JR
FAU - Gasser, T
AU  - Gasser T
FAU - Marconi, R
AU  - Marconi R
FAU - Broussolle, E
AU  - Broussolle E
FAU - Brefel-Courbon, C
AU  - Brefel-Courbon C
FAU - Harhangi, B S
AU  - Harhangi BS
FAU - Oostra, B A
AU  - Oostra BA
FAU - Fabrizio, E
AU  - Fabrizio E
FAU - Bohme, G A
AU  - Bohme GA
FAU - Pradier, L
AU  - Pradier L
FAU - Wood, N W
AU  - Wood NW
FAU - Filla, A
AU  - Filla A
FAU - Meco, G
AU  - Meco G
FAU - Denefle, P
AU  - Denefle P
FAU - Agid, Y
AU  - Agid Y
FAU - Brice, A
AU  - Brice A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (Proteins)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.3.2.27 (parkin protein)
RN  - EC 6.- (Ligases)
SB  - IM
MH  - Binding Sites
MH  - Europe
MH  - Exons/genetics
MH  - Family Health
MH  - Female
MH  - Gene Deletion
MH  - Genes, Recessive/*genetics
MH  - Genotype
MH  - Humans
MH  - *Ligases
MH  - Male
MH  - Mutation
MH  - Parkinson Disease/*genetics
MH  - Pedigree
MH  - Phenotype
MH  - Point Mutation
MH  - Polymorphism, Genetic
MH  - Proteins/*genetics
MH  - *Ubiquitin-Protein Ligases
EDAT- 1999/03/11 00:00
MHDA- 1999/03/11 00:01
CRDT- 1999/03/11 00:00
PHST- 1999/03/11 00:00 [pubmed]
PHST- 1999/03/11 00:01 [medline]
PHST- 1999/03/11 00:00 [entrez]
AID - ddc081 [pii]
AID - 10.1093/hmg/8.4.567 [doi]
PST - ppublish
SO  - Hum Mol Genet. 1999 Apr;8(4):567-74. doi: 10.1093/hmg/8.4.567.