Egeo A, Mazzocco M, Sotgia F, Arrigo P, Oliva R, Bergonòn S, Nizetic D, Rasore-Quartino A, Scartezzini P
Divisione di Pediatria, E.O. Ospedali Galliera, Genova, Italy.
Hum Genet. 1998 Mar;102(3):289-93. doi: 10.1007/s004390050693.
Congenital heart disease (CHD) affects over 40% of Down syndrome (DS) patients. The region proposed to contain the gene(s) for DS CHD has been restricted to 21q22.2-22.3, from D21S55 to MX1. The identification and functional characterization of the genes mapping to this region is a necessary step to understand the pathogenesis of CHD in DS. In an effort to contribute to the construction of a transcriptional map of the DS CHD region we have performed direct cDNA selection using a YAC contig that maps between ETS2 and D21S15 and cDNAs synthesised from fetal heart structures. Here we describe the identification and characterization of a new gene, WRB, that maps to 21q22.3 between ACTL5 and HMG 14 and appears to be widely expressed in adult and fetal tissues. The new gene encodes a basic protein of unknown function containing a tryptophan-rich carboxyl-terminal region and a potential nuclear localization signal. Immunofluorescence analysis shows a predominant localization in the cell nucleus. The understanding of the biological function of the protein product should clarify the potential role of WRB in the pathogenesis of DS CHD.
先天性心脏病（CHD）影响超过40%的唐氏综合征（DS）患者。已提出的包含DS CHD基因的区域被限定在21q22.2 - 22.3，从D21S55到MX1。对定位到该区域的基因进行鉴定和功能表征是理解DS中CHD发病机制的必要步骤。为了有助于构建DS CHD区域的转录图谱，我们使用了一个定位在ETS2和D21S15之间的YAC重叠群以及从胎儿心脏结构合成的cDNA进行了直接cDNA筛选。在此，我们描述了一个新基因WRB的鉴定和表征，该基因定位在21q22.3，位于ACTL5和HMG 14之间，并且似乎在成年和胎儿组织中广泛表达。这个新基因编码一种功能未知的碱性蛋白，该蛋白含有一个富含色氨酸的羧基末端区域和一个潜在的核定位信号。免疫荧光分析显示其主要定位于细胞核。对该蛋白产物生物学功能的了解应能阐明WRB在DS CHD发病机制中的潜在作用。
