Homozygous PINK1 C‐terminus mutation causing early‐onset parkinsonism

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. Ann Neurol 2004;56:427–431

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