Hereditary Benign Intraepithelial Dyskeratosis

遗传性良性上皮内角化不良

• 批准号: 6621699
• 负责人: MICHAEL A HAUSER
• 金额: $ 34.49万
• 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 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6621699
• 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; fluorescent in situ hybridization; gene duplication; high performance liquid chromatography; high throughput technology; human subject; keratin; linkage mapping; molecular cloning; northern blottings; nucleic acid sequence; organ culture; polymerase chain reaction; pulsed field gel electrophoresis; southern blotting; transfection

Hereditary Benign Intraepithelial Dyskeratosis (HBRID) is an autosomal dominant cell proliferation disorder characterized by opaque epithelial plaques on the optical conjuctiva and oral mucosa. The large plaques are elevated, granular, and white to gray in color. They appear at birth or in early childhood, can involve the cornea, and can obstruct the vision. They are also accompanied by hyperemic blood vessels, giving the eye a very red or bloodshot appearance. HBID is found primarily among members of the Haliwa-Saponi Indian Tribe and their relatives. The characteristic "red eye" appearance leads to many difficulties in social interactions and employment, because strangers often presume affected individuals are under the influence of drugs. We have linked the gene for this disorder to chromosome 4q35 with a peak multipoint lod score of 11.58. We have discovered a DNA duplication in this region that is the most likely cause of the disease. In the present application, we propose to extend our investigations into the etiology of this disorder. The role that the DNA duplication plays in HBID will be evaluated by a detailed molecular analysis of the duplicated region and candidate genes. We will also follow the clinical course in affected individuals, using surgical specimens to establish cultured cell lines from conjunctival lesions.

遗传性良性上皮内角化不良 (HBRID) 是一种常染色体显性细胞增殖性疾病，其特征是视神经结膜和口腔粘膜上出现不透明上皮斑块。大斑块升高，呈颗粒状，颜色为白色至灰色。它们出现在出生时或幼儿期，可能累及角膜，并可能阻碍视力。它们还伴有充血的血管，使眼睛呈现非常红色或布满血丝的外观。 HBID 主要发现于哈利瓦-萨波尼印第安部落的成员及其亲属中。典型的“红眼”外观给社交和就业带来了许多困难，因为陌生人常常认为受影响的人受到了毒品的影响。我们已将这种疾病的基因与染色体 4q35 联系起来，其峰值多点 Lod 得分为 11.58。 我们发现该区域的 DNA 重复是导致该疾病的最可能原因。在本申请中，我们建议将我们的研究扩展到这种疾病的病因学。 DNA 复制在 HBID 中所起的作用将通过对复制区域和候选基因的详细分子分析来评估。我们还将跟踪受影响个体的临床病程，使用手术标本从结膜病变中建立培养细胞系。