Screening and characterization of disease gene in del 22q11.2 syndrome.

del 22q11.2综合征疾病基因的筛选和表征。

基本信息

批准号：
09670843
负责人：
MATSUOKA Rumiko
金额：
$ 1.92万
依托单位：
Tokyo Women's Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670843/
关键词：
del 22q11.2 syndrome conotruncal anomaly face syndrome DiGeorge syndrome FISH congenital heart defect cardiovascular anomalies craniofacial defect haploinsufficiency 円錐動脈幹顔貌症候群

项目摘要

To investigate molecular and clinical aspects of conotruncal anomaly face (CAF), we studied the correlation between deletion size and phenotype and the mode of inheritance in 180 conotruncal anomaly face syndrome (CAFS) patients. In CAFS patients, the most frequently observed anomalies were tetralogy of Fallot (TOF) (74%). Conversely, in DiGeorge syndrome (DGS) probands with deletion of 22q11.2, the most frequent cardiovascular anomalies found were interruption of the aortic arch type B (41%), and TOF (29%).Hemizygosity for a region of 22q11.2 was found in 180 (98%) of the patients with CAFS by fluorescent in situ hybridization (FISH), using 20 DiGeorge critical region probes. Ninety-one percent had a distal breakpoint (type-A), 4% had an intermediate breakpoint (type-B), 6% more proximal breakpoints (types C,D and E). All DGS and CAFS patients with schizophrenia fell into the type-A group. No familial cases were found among CAFS patients with absent thymus/DGS, which indicates that extragenic factors may play a role in the genesis of phenotypic variability, especially in patients with cardiovascular anomalies. Also, no difference in deletion size was found among the same family members in the familial CAFS cases, although they had different phenotypes (type-A : 53% ; type-B : 32% ; type-C : 16%). The findings of this study indicated that CAF was almost always associated with the deletion of 22q11.2.The UFDIL gene was deleted in l80patients studied with 22q11.2 deletion, and a smaller deletion of approximately 20 kb that removed exons 1 to 3 of UFDIL was found in one individual with features typical of del 22q11.2 syndrome. These data suggest that UFDIL haploinsufficiency contributes to the congenital heart and craniofacial defects seen in 22q11.2 deletion.

为了研究共鸣异常面部（CAF）的分子和临床方面，我们研究了缺失大小与表型之间的相关性以及180个共鸣异常面部综合征（CAFS）患者的遗传模式。在CAFS患者中，最常观察到的异常是Fallot（TOF）的四边形（74％）。 Conversely, in DiGeorge syndrome (DGS) probands with deletion of 22q11.2, the most frequent cardiovascular anomalies found were interruption of the aortic arch type B (41%), and TOF (29%).Hemizygosity for a region of 22q11.2 was found in 180 (98%) of the patients with CAFS by fluorescent in situ hybridization (FISH), using 20 Digeorge关键区域探针。 91％的远端断点（A型）为中间断点（B），近端断点（C型C，D和E）多6％。所有精神分裂症患者的所有DGS和CAFS患者都属于A型组。在缺乏胸腺/DG的CAFS患者中未发现家族病例，这表明外部因素可能在表型变异性的起源中起作用，尤其是在心血管异常的患者中。同样，在家族CAFS病例中，同一家族成员之间的缺失大小没有差异，尽管它们具有不同的表型（A型A：53％； B型； B型：32％； C型C：16％）。这项研究的结果表明，CAF几乎总是与22q11.2的删除有关。在使用22q11.2删除的L80PATIENT中删除了Ufdil Gene，并且较小的20 kb删除了约20 kb的大约20 kb，从而删除了Exons 1至3的ufdil exons 1至3 ufdil在一个具有DEL 22Q11.2 Syndrome典型功能的ufdil中被发现。这些数据表明，UFDIL单倍体不足促进了22q11.2缺失中的先天性心脏和颅面缺陷。