Molecular characterisation of SGCE-associated myoclonus-dystonia ...

List of content
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LIST OF CONTENT
1 INTRODUCTION..................................................................................... 1
1.1 Movement disorders – dystonia and parkinsonism................................................... 1
1.2 Dystonia......................................................................................................................... 3
1.2.1 SGCE-associated myoclonus-dystonia...................................................... 4
1.2.2 Detection of microdeletions ...................................................................... 6
1.2.3 Maternal imprinting in myoclonus-dystonia ............................................. 7
1.3 Parkinsonism and Parkinson’s disease....................................................................... 7
1.3.1 PINK1-associated Parkinson’s disease...................................................... 9
1.3.2 Heterozygous mutations in Parkinson’s disease ..................................... 11
1.3.3 A common pathway in Parkinson’s disease? .......................................... 12
1.3.4 Nonsense-mediated mRNA decay as a disease mechanism.................... 13
1.4 Mitochondria in Parkinson’s disease........................................................................ 13
1.4.1 The electron transport chain.................................................................... 13
1.4.1.1 Complex I......................................................................................... 14
1.4.1.2 Complex II+III ................................................................................. 14
1.4.1.3 Complex IV...................................................................................... 15
1.4.1.4 Complex V ....................................................................................... 15
1.4.2 Implications of complex I deficiency in Parkinson’s disease ................. 16
1.5 Hypotheses................................................................................................................... 18
2 PATIENTS, MATERIAL AND METHODS ....................................... 19
2.1 Patients ........................................................................................................................ 19
2.1.1 M-D patients with mutations in SGCE and family members.................. 19
2.1.2 PD patients with mutations in PINK1 and controls................................. 20
2.1.2.1 Family W.......................................................................................... 20
2.1.2.2 Other PINK1 mutants....................................................................... 20
2.1.2.3 Healthy controls included in the PINK1 studies.............................. 20
2.2 Material ....................................................................................................................... 23
2.2.1 Chemicals ................................................................................................ 23
2.2.2 Solutions.................................................................................................. 25
2.2.3 Kits .......................................................................................................... 26
2.2.4 Antibodies ............................................................................................... 26
2.2.5 Oligonucleotides...................................................................................... 27