培训课件--卢彦平产前诊断相关技术及其临床应用简介.ppt

Meckel 综合征--TCTN2基因突变 301医院 Joubert 综合征 临床症状包括肌张力减退、共济失调、精神发育迟缓及动眼运动障碍、新生儿呼吸异常等。 脑部核磁标志性特征为“磨牙征”(小脑吲部发育不全或缺失，小脑上脚增宽，后颅窝加深的征象)。 Joubert综合征相关病症 Joubert并不同程度的累及其它器官，主要是肾和眼，尚有多指、肝脏纤维化等。 Joubert综合征 (JBTS) case： 第一孩儿童医院诊断Joubert综合征 二代测序找到突变（CEP290) 再次怀孕超声提示胎儿小脑蚓部缺失 引产同时基因检测证实与先证者携带相同的基因突变 多囊肾 婴儿型多囊肾：PKHD1 多囊肾可以是其它初级纤毛疾病的表型之一 case： 孕期胎儿双侧多囊肾，羊水少，怀疑婴儿型多囊肾，引产基因检测没有发现PKHD1突变，结果发现AHI1基因突变，此基因可以引起Joubert 综合征及Meckel 综合征 提示发现多囊肾时要仔细检查其他部位，尤其是脑部 全外显子组测序 先天性关节挛缩病例 两个异常孩子死亡，没有留下 DNA ？ 1500个基因，没有发现异常 全外显子组？ ECEL1基因突变 Am J Med Genet A. 2015 Apr;167A(4):731-43. doi: 10.1002/ajmg.a.37018. Epub 2015 Feb 23. ECEL1 mutation causes fetal arthrogryposis multiplex congenita. 早孕晚期超声已经诊断 全外子组测序发现ECEL1基因突变 .Arthrogryposis multiplex congenita (AMC) is a descriptor for the clinical finding of congenital fixation of multiple joints. We present a consanguineous healthy couple with two pregnancies described with AMC due to characteristic findings on ultrasonography of fixated knee extension and reduced fetal movement at the gestational age of 13 weeks + 2 days and 12 weeks + 4 days. Both pregnancies were terminated and postmortem examinations were performed. The postmortem examinations confirmed AMC and suggested a diagnosis of centronuclear myopathy (CNM) due to characteristic histological findings in muscle biopsies. Whole exome sequencing (WES) was performed on all four individuals and the outcome was filtered by application of multiple filtration parameters satisfying a recessive inheritance pattern. Only one gene, ECEL1, was predicted damaging and had previously been associated with neuromuscular disease or AMC. The variant found ECEL1 is a missense mutation in a highly conserved residue and was predicted pathogenic by prediction software. Expanding the phenotypic spectrum of ECEL1-related congenital contracture syndromes. Shaaban S1, Duzcan F, Yildirim C, Chan WM, Andrews C, Akarsu NA, Engle EC.