Funke B, Pandita R K, Morrow B E
Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
Genomics. 2001 May 1;73(3):264-71. doi: 10.1006/geno.2000.6506.
Three congenital disorders, cat-eye syndrome (CES), der(22) syndrome, and velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), result from tetrasomy, trisomy, and monosomy, respectively, of part of 22q11. They share a 1.5-Mb region of overlap, which contains 24 known genes. Although the region has been sequenced and extensively analyzed, it is expected to contain additional genes, which have thus far escaped identification. To understand completely the molecular etiology of VCFS/DGS, der(22) syndrome, and CES, it is essential to isolate all genes in the interval. We have identified and characterized a novel human gene, located within the 1.5-Mb region deleted in VCFS/DGS, trisomic in der(22) syndrome and tetrasomic in CES. The deduced amino acid sequence of the human gene and its mouse homologue contain several WD40 repeats, but lack homology to known proteins. We termed this gene WDR14 (WD40 repeat-containing gene deleted in VCFS). It is expressed in a variety of human and mouse adult and fetal tissues with substantial expression levels in the adult thymus, an organ hypoplastic in VCFS/DGS.
三种先天性疾病，猫眼综合征（CES）、der(22)综合征以及心脏-颜面-综合征/迪格奥尔格综合征（VCFS/DGS），分别由22q11部分区域的四体性、三体性和单体性导致。它们共享一个1.5兆碱基的重叠区域，该区域包含24个已知基因。尽管该区域已被测序并进行了广泛分析，但预计还包含其他尚未被识别的基因。为了全面了解VCFS/DGS、der(22)综合征和CES的分子病因，分离该区间内的所有基因至关重要。我们已经鉴定并表征了一个新的人类基因，它位于VCFS/DGS中缺失的1.5兆碱基区域内，在der(22)综合征中为三体状态，在CES中为四体状态。该人类基因及其小鼠同源物推导的氨基酸序列包含几个WD40重复序列，但与已知蛋白质缺乏同源性。我们将这个基因命名为WDR14（在VCFS中缺失的含WD40重复序列的基因）。它在多种人类和小鼠的成年及胎儿组织中表达，在成年胸腺中表达水平较高，而胸腺在VCFS/DGS中发育不全。
