HEREDITARY BENIGN INTRAEPITHELIAL DYSKETATOSIS

遗传性良性上皮内酮症

• 批准号: 2451356
• 负责人: JEFFERY Marvin VANCE
• 金额: $ 24.46万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2451356
• 关键词: Native Americans; artificial chromosomes; autosomal dominant trait; cell line; cell proliferation; clinical research; congenital eye disorder; conjunctiva; disease /disorder etiology; family genetics; genetic mapping; human subject; keratin; linkage mapping

DESCRIPTION: Hereditary Benign Intraepithelial Dyskeratosis (HBID) is an autosomal dominant, cell proliferation disorder characterized by intraepithelial dyskeratosis of the conjunctiva of the eye and oral mucosa, producing opaque epithelial plaques. HBID is found primarily in members of the Native American Haliwa-Saponi Indian Tribe and their relatives, which include individuals of African American and Caucasian descent. This disorder, which can lead to blindness, also has reported seasonal variations, suggesting environmental interactions as well. The PI has identified 2 branches of a large (over 350 individuals), inbred Haliwa-Saponi family with HBID, representing a single founding mutation. Identification of the HBID gene defect will allow initiation of studies into effective treatment of this disorder and provide information into the normal mechanisms of cell proliferation. The investigator has already collected 46 individuals (24 affected) from this large family and had excluded the 2 keratin clusters as candidate genes, that are defected in a similar disorder (White Spong Nevus). The principal investigator proposes to identify, examine and collect additional members of this family for pedigree linkage analysis to establish its chromosomal localization. Clinical characterization of the disorder, its extent and seasonal variation will be examined. Cell lines of conjunctival epithelium from affecteds will be established and evaluated. Once linkage is established, fine mapping of the gene will be performed using the combinations and haplotype analysis. Physical contigs of YAC'S and PAC'S will be formed across the minimal candidate region and used to identify candidate genes. These will be evaluated and the gene for HBID will be identified and the protein characterized.

描述：遗传性良性上皮内角化不良 (HBID) 是一种 常染色体显性遗传，细胞增殖障碍，其特征为 眼结膜和口腔粘膜上皮内角化不良， 产生不透明的上皮斑块。 HBID 主要见于以下成员 美洲原住民哈利瓦-萨波尼印第安部落及其亲戚 包括非裔美国人和白种人后裔。 这 也有报道称，这种疾病可能导致失明 变化，表明环境相互作用。 该PI有 确定了一个大型近交系（超过 350 个个体）的 2 个分支 具有 HBID 的 Haliwa-Saponi 家族，代表单一创始突变。 HBID 基因缺陷的鉴定将允许启动以下研究： 有效治疗这种疾病并为正常情况提供信息 细胞增殖的机制。 调查人员已收集了 46 名个体（24 名受影响者） 这个大家族并排除了 2 个角蛋白簇作为候选 基因，在类似疾病（白色海绵痣）中存在缺陷。 这 首席研究员建议识别、检查和收集额外的 该家族的成员进行谱系连锁分析，以确定其 染色体定位。 该疾病的临床特征、其 将检查范围和季节变化。 结膜细胞系 将建立并评估受影响者的上皮。 一次联动 建立后，将使用 组合和单倍型分析。 YAC'S 和 PAC'S 的物理重叠群 将在最小候选区域中形成并用于识别 候选基因。 这些将被评估并且 HBID 基因将被 鉴定并表征蛋白质。