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Late onset sporadic Parkinson's disease caused by PINK1 mutations: Clinical and functional study
Author(s) -
Gelmetti Vania,
Ferraris Alessandro,
Brusa Livia,
Romano Francesca,
Lombardi Federica,
Barzaghi Chiara,
Stanzione Paolo,
Garavaglia Barbara,
Dallapiccola Bruno,
Valente Enza Maria
Publication year - 2008
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.21960
Subject(s) - parkinsonism , pink1 , parkin , parkinson's disease , age of onset , proband , disease , medicine , phenotype , dyskinesia , compound heterozygosity , mutation , genetics , biology , gene
Homozygous or compound heterozygous mutations in the PINK1 gene represent the second most frequent cause of autosomal recessive parkinsonism after Parkin . The phenotype differs from idiopathic Parkinson's disease for earlier onset, slower disease progression, and better response to therapy. Indeed, the rare patients with onset above 50 years are usually relatives of early‐onset probands. Here, we report the first occurrence of compound heterozygous PINK1 mutations in a sporadic patient with a phenotype indistinguishable from idiopathic Parkinson's disease (PD), with onset in the late seventh decade, rapid progression and good response to levodopa that waned with time. Both mutations (p.A244G and p.V317I) were found to abolish the protective effect of wild‐type PINK1 against staurosporine‐induced apoptosis. These findings further expand the clinical spectrum of PINK1 ‐related parkinsonism to include late onset, typical PD, and underline the existing difficulties in discriminating between mendelian parkinsonism and idiopathic PD. © 2008 Movement Disorder Society