Homozygous PINK1 C-terminus mutation causing early-onset parkinsonism.

Department of Clinical Genetics, Erasmus MC Rotterdam, The Netherlands.
Annals of Neurology (Impact Factor: 11.91). 10/2004; 56(3):427-31. DOI: 10.1002/ana.20247
Source: PubMed

ABSTRACT Two homozygous mutations in the PINK1 gene, encoding a mitochondrial putative protein kinase, recently have been identified in families with PARK6-linked, autosomal recessive early-onset parkinsonism (AREP). Here, we describe a novel homozygous mutation (1573_1574 insTTAG) identified in an AREP patient, which causes a frameshift and truncation at the C-terminus of the PINK1 protein, outside the kinase catalytic domain. The clinical phenotype includes early-onset (28 years) parkinsonism, foot dystonia at onset, good levodopa response, slow progression, early levodopa-induced dyskinesias, and sleep benefit, thereby resembling closely parkin-related disease. These findings confirm that recessive mutations in PINK1 cause early-onset parkinsonism and expand the associated clinical phenotype.

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    10/2006, Degree: Doctoral degree in genetic epidemiology, Supervisor: Professor CM van Duijn