CRI DU CHAT SYNDROME: GENE IDENTIFICATION

描述：Cri-du-chat综合征是一种被广泛描述的部分异染色体 由5号染色体短臂缺失引起。 患者 这种综合征表现为小头畸形、圆脸、距过远， 小颌畸形，鼻梁突出，内眦赘皮，张力减退， 严重精神病和智力迟钝。 通过描述 超过50名患者存在5 p缺失，这是一个染色体区域，长度为2 Mbp， 5p15.2和参与猫叫的染色体片段已经被 定位到5 p15的750个区域。两个区域的YAC重叠群已经被 已经鉴定了跨越每个区域的完整的和非嵌合的YACS。 虽然这项建议的长期目标是确定基因，当 存在于一个副本中，导致与 cri-du-chat综合征，最初的目标将是开发一个转录 该区域的地图，以便根据其 相对于Cri-du-chat临界区域的位置。 的战略 确定这些基因首先是继续与表征 具有小5 p缺失或部分cri-du-chat表型的患者， 这两个临界区域可以进一步变窄。 二是建设 将完成已启动的粘粒重叠群的构建。 第三、 确定关键区域内基因定位的几种方法 包括EST作图、cDNA选择、外显子捕获和 克隆HTF岛。 在执行筛选策略以确定 来自相同基因的克隆， 将研究独特的基因。 此次调查将包括 研究人成人和胎儿组织中的表达水平， 以及在不同鼠妊娠阶段中的表达水平。 的 这些基因的初步鉴定将鉴定候选基因， 可能参与了基于Cri-du-chat综合征的临床病因学 基因是否在胎儿发育过程中表达。

DESCRIPTION: The cri-du-chat syndrome is a well-described partial aneusomy resulting from the deletion of the short arm of chromosome 5. Patients with this syndrome present with microcephaly, a round face, hypertelorism, micrognathia, prominent nasal bridge, epicanthal folds, hypotonia, and severe psychomotor and mental retardation. Through the characterization of over 50 patients with 5p deletions, a chromosomal region that is 2 Mbp in 5p15.2 and the chromosomal segment involved in the cat-like cry has been mapped to a 750 region of 5p15.3 YAC contigs of both regions have been completed and nonchimeric YACS that span each region have been identified. While the long term goal of this proposal is to identify genes that, when present in one copy, cause the clinical features associated with the cri-du-chat syndrome, the initial goal will be to develop a transcriptional map of the region in order to identify candidate genes based on their location with respect to the cri-du-chat critical regions. The strategy to identify these genes is first to continue with the characterization of patients with small 5p deletions or partial cri-du-chat phenotypes such that the two critical regions can be further narrowed. Second, the construction of a cosmid contig which has been initiated will be completed. Third, several approaches to identify the genes mapping within the critical regions will be performed and include EST mapping, cDNA selection, exon-trapping and cloning HTF islands. After performing screening strategies to identify clones that are derived from the same gene, the pattern of expression of unique genes will be investigated. This investigation will include investigating the level of expression in human adult and fetal tissues as well as the level of expression in different murine gestational stages. The initial characterization of these genes will identify candidate genes that may be involved in the clinical etiology of the cri-du-chat syndrome based on whether a gene is expressed during fetal development.