Clinical findings in a large family with a parkin ex3delta40 mutation.
OBJECTIVE
To describe a large consanguineous family in which inheritance of a 438- to 477-base pair deletion in exon 3 (Ex3Delta40) in the parkin gene resulted in parkinsonism (age range at onset, 24-32 years).


METHODS
Fifty-two family members underwent genetic analysis.


METHODS
Two clinical examiners blinded to genetic status evaluated 21 family members, including all mutation carriers (4 homozygous and 12 heterozygous individuals; 5 family members did not have the mutation).


RESULTS
In this family, the parkin Ex3Delta40 mutation is recessive; only homozygotes manifest symptoms of early-onset levodopa-responsive parkinsonism, including resting tremor, dystonia, and slow progression, with the caveat that presymptomatic signs of dopaminergic loss in heterozygotes must be excluded by fluorodopa F 18 with positron emission tomography. This contrasts with the autosomal dominant pattern of inheritance of parkinsonism described in families with the same mutation.


CONCLUSIONS
In families with a dominant inheritance, an additional genetic or environmental cause must coexist with the Ex3Delta40 mutation.
Munhoz
Renato P
RP
Movement Disorders Centre, Toronto Western Hospital, and Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Sa
Daniel S
DS
Rogaeva
Ekaterina
E
Salehi-Rad
Shabnam
S
Sato
Christine
C
Medeiros
Helena
H
Farrer
Matthew
M
Lang
Anthony E
AE
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000503:physiopathology*; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
D044767:Ubiquitin-Protein Ligases; C111567:parkin protein