medical genetics-pp2014(研).pptVIP

* Leigh syndrome 多见于婴幼儿,因线粒体能量代谢障碍导致中枢神经系统进行性退行性损害,临床表现复杂,病理特征为脑基底节、脑干海绵样变性 喂养困难,营养不良,进行性运动倒退,肌张力低下,眼震. 死于呼吸衰竭。 脑MR I显示双侧基底节对称性损害,脑干、小脑萎缩 * ， X * * Short and broad hands, big toe widely spaced, palm crease * * 嘴大，唇厚，腭弓高 * 。 * 发 * The X Chromatin( the Barr body) 46,XX 46,XY 46,XXX The Lyon hypothesis In the somatic cells of female mammals, only one X chromosome is transcriptionally active. The second X is heterochromatic and inactive and appears in interphase cells as sex chromatin, the Barr body. Inactivation occurs early in embryonic life. In any one female somatic cell, the inactive X may be either the paternal or the maternal X, namely the inactivation is randomly. Mary F. Lyon （1961） Random X-chromosome Inactivation occurs early in embryonic life The X inactivation center has been mapped to proximal Xq, in the band Xq13. The XIST gene is expressed only from the allele on the inactive X; It is transcriptionally silent on the active X in both male and female cells. The X Inactivation Center (XIC)  and the XIST Gene The X Inactivation Center (XIC) and the XIST Gene Xq13 Nonrandom X Inactivation Karyotype 47,XXY 1/1000 male live births 80% 48,XXXY 1/25,000 males 48,XXYY 49,XXXYY 1/1000 males mosaics 15% 46, XY/47, XXY 或 46, XY/48, XXXY Klinefelter Syndrome Clinical Features Klinefelter syndrome (47, XXY) Etiology of Klinefelter Syndrome Paternal meiosis I 1/2 Maternal meiosis I 1/3 Maternal meiosis II / postzygotic mitosis remainder Nondisjunction of the X and the Y Turner syndrome (45, X) Clinical Features Clinical Features Clinical Features Clinical Features spontaneous abortions 99% Karyotype Incidence 46, fra (X) Y 1/4000 males 1/4000 - 8000 females Fragil