Positional Cloning of New Disease Genes for Kallmann Syndrome and Potocki- Shaffer Syndrome ; Positionelle Klonierung der Krankheitsgene für Kallmann Syndrom und Potocki- Shaffer Syndrom

Contents Dedication --- vi Figures --- vii 1\. Aim of the thesis --- 1 1.1 Kallmann syndrome --- 1 1.2 Potocki-Shaffer syndrome --- 1 2\. List of original publications --- 2 2.1 Paper I --- 3 2.2 Paper II --- 4 2.3 Paper III --- 5 2.4 Paper IV --- 6 3\. ASHG Abstract --- 7 4\. Introduction --- 8 4.1 Balanced translocations: visible bridges between genotypes and phenotypes --- 8 4.2 Structural chromosome rearrangements --- 10 4.3 A historical perspective: balanced translocations and positional cloning --- 13 4.4 Balanced translocations associated with abnormal phenotypes-- 16 4.5 Balanced translocations in recessive disorders --- 19 4.6 Positional effect --- 19 4.7 Balanced translocation as a “double hit” --- 21 4.8 Balanced translocations with discordant phenotype --- 21 4.9 Balanced translocations involving the X chromosome --- 23 5\. Kallmann syndrome --- 26 5.1 Introduction --- 26 5.2 Genetics --- 28 5.3 Subjects --- 29 5.3.1 Positional cloning of t(7;8)(p12.3;p11.2)dn --- 29 5.3.2 Candidate gene approach with CHD7 --- 29 5.3.3 Positional cloning of t(10;12)(q26.12;q13.11)dn --- 30 5.4 Hypothesis --- 30 5.4.1 Positional cloning of t(7;8)(p12.3;p11.2)dn --- 30 5.4.2 Candidate gene approach with CHD7 --- 31 5.4.3 Positional cloning of t(10;12)(q26.12;q13.11)dn --- 32 5.5 Results and Discussion --- 32 5.5.1 Positional cloning of t(7;8)(p12.3;p11.2)dn --- 32 5.5.2 Candidate gene approach with CHD7 --- 36 5.5.3 Positional cloning of t(10;12)(q26.12;q13.11)dn --- 40 6\. Potocki- Shaffer syndrome --- 45 6.1 Introduction and Genetics --- 45 6.2 Subjects --- 46 6.2.1 DGAP012 patient with t(11;19)(p11.2;p13.2)dn --- 46 6.2.2 MCN1762 patient with t(1;11)(p13;p11.2)dn --- 47 6.2.3 GM03316 --- 48 6.3 Hypothesis --- 49 6.4 Results --- 49 6.4.1 PHF21A is disrupted in unrelated subjects with chromosomal translocations, ID, and CFA --- 49 6.4.2 PHF21A maps to the critical PSS interval associated with ID and CFA --- 51 6.4.3 Murine Phf21a is expressed in the CNS and cranial bones --- 53 6.4.4 Suppression of zebrafish phf21a ...