Familial Amyloidosis with Polyneuropathy Studies of genetic factors modifying the phenotype of the disease

................................................................................................. 6 List of papers .......................................................................................... 7 Populärvetenskaplig Sammanfattning ................................................... 8 Abbreviations ....................................................................................... 10 Introduction .......................................................................................... 11 Basic Molecular Genetics ........................................................................................... 11 Mitochondrial Genetics .............................................................................................. 12 Mitochondrial haplogroups .................................................................................. 13 Sequence variations .................................................................................................... 14 Inherited Genetic disorders ....................................................................................... 14 Familial amyloidosis with polyneuropathy ............................................................... 15 Transthyretin gene and protein ........................................................................... 15 Mutations ............................................................................................................... 16 Val30Met .......................................................................................................................... 16 Symptoms ............................................................................................................... 16 Treatment ............................................................................................................... 17 V30M variations between and within populations ................................................... 17 V30M Carrier frequency (Prevalence) ................................................................. 18 Phenotype variations ............................................................................................ 18 Age at onset ...................................................................................................................... 18 Penetrance ........................................................................................................................ 19 Homozygous carriers ........................................................................................................ 19 Parent-of-origin and Anticipation ...................................................................... 20 Population Founder effects of the TTR V30M mutation .................................... 20 Other influencing factors .......................................................................................... 20 Mitochondrial effect .............................................................................................. 21 Regulatory Regions within and surrounding the TTR gene............................... 21 MicroRNA ......................................................................................................................... 21 Aim ...................................................................................................... 23 The aims were: ........................................................................................................... 23 Paper I ................................................................................................................... 23 Paper II .................................................................................................................. 23 Paper III ................................................................................................................ 23 Paper IV ................................................................................................................. 23 Paper V .................................................................................................................. 23 Methodology ........................................................................................ 24 Patient material and control material ...................................................................... 24