OBJECTIVE: To investigate the association between parkin gene mutations and parkinsonism in an Italian family in which three of 12 siblings born to first-degree consanguineous parents had early-onset parkinsonism. BACKGROUND: Several deleting or truncating mutations as well as missense mutations of the parkin gene were associated with early-onset parkinsonism. METHOD: Three brothers were examined clinically at several stages of the disease. Single-strand conformational polymorphism analysis was done on the parkin gene of 32 members of the family. Samples showing mobility shifts were considered for mutation analysis. RESULTS: Direct DNA sequencing revealed a novel homozygous amino acid substitution, Arg42Pro, in all three patients compared with a control DNA sample. The mutation occurred in the ubiquitinlike domain at the N-terminal of the protein. The patients did not display the clinical hallmarks previously seen with parkin mutations and were indistinguishable from patients with sporadic PD. CONCLUSIONS: These findings confirm the recessive character of parkin mutations causing early-onset parkinsonism and the essential role of the ubiquitinlike region, highly conserved among species, and in accordance with the proposed parkin function.
OBJECTIVE: To investigate the association between parkin gene mutations and parkinsonism in an Italian family in which three of 12 siblings born to first-degree consanguineous parents had early-onset parkinsonism. BACKGROUND: Several deleting or truncating mutations as well as missense mutations of the parkin gene were associated with early-onset parkinsonism. METHOD: Three brothers were examined clinically at several stages of the disease. Single-strand conformational polymorphism analysis was done on the parkin gene of 32 members of the family. Samples showing mobility shifts were considered for mutation analysis. RESULTS: Direct DNA sequencing revealed a novel homozygous amino acid substitution, Arg42Pro, in all three patients compared with a control DNA sample. The mutation occurred in the ubiquitinlike domain at the N-terminal of the protein. The patients did not display the clinical hallmarks previously seen with parkin mutations and were indistinguishable from patients with sporadic PD. CONCLUSIONS: These findings confirm the recessive character of parkin mutations causing early-onset parkinsonism and the essential role of the ubiquitinlike region, highly conserved among species, and in accordance with the proposed parkin function.
Authors: Viduth K Chaugule; Lynn Burchell; Kathryn R Barber; Ateesh Sidhu; Simon J Leslie; Gary S Shaw; Helen Walden Journal: EMBO J Date: 2011-06-21 Impact factor: 11.598
Authors: Helen C Ardley; Gina B Scott; Stephen A Rose; Nancy G S Tan; Alexander F Markham; Philip A Robinson Journal: Mol Biol Cell Date: 2003-08-22 Impact factor: 4.138