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Clinical Findings in a Large Family With a Parkin Ex340 Mutation

Renato P. Munhoz, MD; Daniel S. Sa, MD; Ekaterina Rogaeva, PhD; Shabnam Salehi-Rad, BSc; Christine Sato, BSc; Helena Medeiros, BA; Matthew Farrer, PhD; Anthony E. Lang, MD, FRCPC

Arch Neurol. 2004;61:701-704.

Objective  To describe a large consanguineous family in which inheritance of a 438– to 477–base pair deletion in exon 3 (Ex340) in the parkin gene resulted in parkinsonism (age range at onset, 24-32 years).

Design  Fifty-two family members underwent genetic analysis.

Main Outcome Measure  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 Ex340 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.

Conclusion  In families with a dominant inheritance, an additional genetic or environmental cause must coexist with the Ex340 mutation.

From the Movement Disorders Centre, Toronto Western Hospital (Drs Munhoz, Sa, and Lang), and Centre for Research in Neurodegenerative Diseases (Dr Rogaeva and Mss Salehi-Rad, Sato, and Medeiros), University of Toronto, Toronto, Ontario; and the Department of Neuroscience, Mayo Clinic, Jacksonville, Fla (Dr Farrer).

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