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Mutational screening of the parkin gene among South Indians with early onset Parkinson's disease

Sree Chitra Tirunal Institute for Medical Sciences and Technology, Tiruvananantapuram, Kerala, India
Journal of Neurology Neurosurgery & Psychiatry (Impact Factor: 5.58). 12/2005; 76(11):1588-90. DOI: 10.1136/jnnp.2004.046888
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ABSTRACT Parkin mutations are commonly encountered in multiethnic populations with familial early onset Parkinson's disease (PD) and less frequently in sporadic PD. A total of 102 patients (recruited from a hospital) with early onset PD from an ethnically homogeneous Indian population (age of onset < or =50 years) including both familial (n = 20) and sporadic (n = 82) cases were screened for parkin mutations. There were 105 normal controls. A homozygous missense mutation, Thr240Met, was found in exon 6 of one case and homozygous deletions of exons 8 and 9 were found in another index case. These constituted 2% of all early onset PD, 10% of all familial early onset PD, and 25% of all autosomal recessive early onset PD patients. No mutations were found in the patients with sporadic early onset PD, but seven exonic changes (three novel) were identified among 23 sporadic cases. These may represent heterozygous pathogenic changes. Use of more advanced techniques, including gene dosage estimation, and studies in Indian populations of different ethnic backgrounds may detect more mutations in future studies. This is the first report of parkin mutations from India and the first report from a non-white, non-oriental population of early onset PD.

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    • "The Val380Leu mutation has, in previous studies, been found in both healthy and affected individuals. Abbas et al. [17] reported that the substitution was found in eleven European families and also 16% of the control subjects and it appear to be common across populations [52,54] and therefore not considered a main cause of disease development. It might, however, alter the Parkin protein and contribution to the pathogenesis of idiopathic PD, as noted in a study by Lucking et al. [55], which reported homozygous Val380Leu substitutions to be associated with sporadic PD. "
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