by Keung Wing Ying. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1998. / Includes bibliographical references (leaves 115-128). / Abstract also in Chinese. / Abstract --- p.I / Acknowledgments --- p.IV / Abbreviations --- p.V / List of Tables --- p.VII / List of Figures --- p.VIII / Chapter Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Familial Adenomatous Polyposis (FAP) --- p.1 / Chapter 1.1.1 --- Occurrence and prevalence --- p.1 / Chapter 1.1.2 --- Clinical features --- p.2 / Chapter 1.1.3 --- Laboratory studies --- p.5 / Chapter 1.1.4 --- Diagnosis --- p.6 / Chapter 1.1.5 --- Management --- p.8 / Chapter 1.2 --- Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE) --- p.8 / Chapter 1.2.1 --- Clinical features --- p.9 / Chapter 1.2.2 --- Pathogenesis --- p.11 / Chapter 1.2.3 --- Histology --- p.12 / Chapter 1.2.4 --- Differential diagnosis --- p.13 / Chapter 1.2.5 --- CHRPE as an early clinical marker for FAP --- p.14 / Chapter 1.3 --- The Adenomatous Polyposis Coli (APC) Gene --- p.16 / Chapter 1.3.1 --- Discovery --- p.16 / Chapter 1.3.2 --- Structure and function --- p.17 / Chapter 1.3.3 --- Sequence alterations in the APC gene --- p.18 / Chapter 1.3.4 --- APC mutations associated with specific clinical features --- p.21 / Chapter 1.3.5 --- APC gene mutations in Chinese --- p.22 / Chapter 1.3.6 --- Methods for detecting mutation in the APC gene and linkage analysis --- p.23 / Chapter Chapter 2 --- Study Objectives --- p.44 / Chapter Chapter 3 --- Methodology --- p.45 / Chapter 3.1 --- Subjects --- p.45 / Chapter 3.2 --- CHRPE analysis --- p.45 / Chapter 3.2.1 --- Ophthalmoscopic examination --- p.45 / Chapter 3.2.2 --- Diagnostic criteria of CHRPE --- p.45 / Chapter 3.3 --- Materials and Equipment --- p.46 / Chapter 3.3.1 --- Enzymes --- p.46 / Chapter 3.3.2 --- DNA markers --- p.46 / Chapter 3.3.3 --- Reagent kits --- p.46 / Chapter 3.3.4 --- Primers for PCR --- p.46 / Chapter 3.3.5 --- Chemicals and reagents --- p.47 / Chapter 3.3.6 --- Radioisotopes --- p.47 / Chapter 3.3.7 --- Solutions and buffers --- p.47 / Chapter 3.3.8 --- Equipment --- p.48 / Chapter 3.4 --- Methods --- p.49 / Chapter 3.4.1 --- Blood collection --- p.49 / Chapter 3.4.2 --- DNA extraction --- p.49 / Chapter 3.4.3 --- DNA quantitation --- p.50 / Chapter 3.4.4 --- Polymerase Chain Reaction (PCR) --- p.50 / Chapter 3.4.5 --- Agarose gel electrophoresis --- p.51 / Chapter 3.4.6 --- Single Strand Conformation Polymorphism (SSCP) --- p.52 / Chapter 3.4.7 --- Direct DNA sequencing --- p.52 / Chapter 3.4.8 --- Analysis of microsatellite markers --- p.54 / Chapter Chapter 4 --- Results --- p.59 / Chapter 4.1 --- Study subjects --- p.59 / Chapter 4.1.1 --- FAP index patients --- p.59 / Chapter 4.1.2 --- FAP families --- p.59 / Chapter 4.1.3 --- Control subjects with CHRPE only --- p.60 / Chapter 4.1.4 --- Normal control subjects --- p.60 / Chapter 4.2 --- CHRPE analysis --- p.60 / Chapter 4.2.1 --- CHRPE in FAP index patients --- p.60 / Chapter 4.2.2 --- CHRPE in family members --- p.61 / Chapter 4.2.3 --- CHRPE in controls subjects --- p.61 / Chapter 4.2.4 --- Statistical analysis --- p.61 / Chapter 4.3 --- PCR optimization --- p.62 / Chapter 4.4 --- SSCP analysis of the APC gene --- p.62 / Chapter 4.5 --- Direct DNA sequencing analysis --- p.63 / Chapter 4.5.1 --- Nonsense mutations --- p.63 / Chapter 4.5.2 --- Novel silent mutations --- p.64 / Chapter 4.5.3 --- Polymorphisms --- p.65 / Chapter 4.6 --- Haplotype analysis --- p.67 / Chapter 4.7 --- Family studies --- p.67 / Chapter 4.7.1 --- Family A --- p.67 / Chapter 4.7.2 --- Family B --- p.68 / Chapter 4.7.3 --- Family C --- p.68 / Chapter 4.7.4 --- Family D --- p.69 / Chapter 4.7.5 --- Family E --- p.70 / Chapter 4.7.6 --- Family F --- p.70 / Chapter Chapter 5 --- Discussion --- p.104 / Chapter 5.1 --- The predictive value of CHRPE in FAP patients and family members --- p.104 / Chapter 5.2 --- The laboratory techniques in this study --- p.105 / Chapter 5.2.1 --- PCR optimization --- p.105 / Chapter 5.2.2 --- Single Strand Conformation Polymorphism (SSCP) --- p.106 / Chapter 5.2.3 --- Direct DNA sequencing --- p.107 / Chapter 5.3 --- Novel mutation in the APC gene --- p.108 / Chapter 5.4 --- Reported mutations in the APC gene --- p.108 / Chapter 5.4.1 --- 3183del5 --- p.108 / Chapter 5.4.2 --- R216X and R283X --- p.109 / Chapter 5.5 --- Novel silent mutations and polymorphisms in the APC gene --- p.109 / Chapter 5.5.1 --- Novel silent mutations --- p.109 / Chapter 5.5.2 --- Polymorphisms --- p.110 / Chapter 5.6 --- The relationship between APC gene mutations and CHRPE --- p.111 / Chapter 5.7 --- Haplotype analysis --- p.112 / Chapter Chapter 6 --- Conclusion --- p.114 / Chapter Chapter 7 --- References --- p.115