Wright T J, Ricke D O, Denison K, Abmayr S, Cotter P D, Hirschhorn K, Keinänen M, McDonald-McGinn D, Somer M, Spinner N, Yang-Feng T, Zackai E, Altherr M R
Life Sciences Division, Los Alamos National Laboratory, NM 87545, USA.
Hum Mol Genet. 1997 Feb;6(2):317-24. doi: 10.1093/hmg/6.2.317.
Wolf-Hirschhorn syndrome (WHS) is a multiple malformation syndrome characterised by mental and developmental defects resulting from the absence of a segment of one chromosome 4 short arm (4p16.3). Due to the complex and variable expression of this disorder, it is thought that the WHS is a contiguous gene syndrome with an undefined number of genes contributing to the phenotype. In an effort to identify genes that contribute to human development and whose absence results in this syndrome, we have utilised a series of landmark cosmids to characterise a collection of WHS patient derived cell lines. Fluorescence in situ hybridisation with these cosmids was used to refine the WHS critical region (WHSCR) to 260 kb. The genomic sequence of this region is available and analysis of this sequence through BLAST detected several cDNA clones in the dbEST data base. A total of nine independent cDNAs, and their predicted translation products, from this analysis show no significant similarity to members of DNA or protein databases. Furthermore, these genes have been localised within the WHS critical region and reveal an interesting pattern of transcriptional organisation. A previously published report of a patient with proximal 4p- syndrome further refines the WHSCR to 165 kb defined by the loci D4S166 and D4S3327. This work provides the starting point to understand how multiple genes or other mechanisms can contribute to the complex phenotype associated with the Wolf-Hirschhorn syndrome.
沃尔夫-赫希霍恩综合征（WHS）是一种多发畸形综合征，其特征为因一条4号染色体短臂（4p16.3）的一段缺失而导致的智力和发育缺陷。由于该病症表现复杂且具有变异性，人们认为WHS是一种邻接基因综合征，有数量不明的基因对该表型有影响。为了鉴定对人类发育有影响且其缺失会导致该综合征的基因，我们利用了一系列标志性黏粒来对一组源自WHS患者的细胞系进行特征分析。用这些黏粒进行荧光原位杂交，将WHS关键区域（WHSCR）定位到了260 kb。该区域的基因组序列是已知的，通过BLAST对该序列进行分析，在dbEST数据库中检测到了几个cDNA克隆。此次分析共得到9个独立的cDNA及其预测的翻译产物，它们与DNA或蛋白质数据库中的成员没有明显的相似性。此外，这些基因已被定位在WHS关键区域内，并揭示了一种有趣的转录组织模式。之前发表的一篇关于一名近端4p-综合征患者的报告进一步将WHSCR定位到了由基因座D4S166和D4S3327界定的165 kb区域。这项工作为理解多个基因或其他机制如何导致与沃尔夫-赫希霍恩综合征相关的复杂表型提供了起点。
