Age-related macular degeneration - Clinical features in a large family and linkage to chromosome 1q
Age-related macular degeneration - Clinical features in a large family and linkage to chromosome 1q
复制标题
DOI：
10.1001/archopht.116.8.1082
复制
发表时间：
1998-08-01
影响因子：
--
通讯作者：
Acott, TS
中科院分区：
文献类型：
--
作者：
Klein, ML;Schultz, DW;Acott, TS
目的：目的：确定一个年龄相关性黄斑变性（ARMD）家系的致病基因的染色体定位，描述该家系的临床特征。方法：对一个ARMD家系进行研究，采用眼底立体照相法记录家系成员的病情，并采用改良的威斯康星州黄斑相关性黄斑病变分级系统进行分级。使用DNA合并策略结合共享片段分析，以约6厘摩间距进行全基因组筛选，以确定可能的染色体区域。整个家庭，然后在每个可能的位点进行筛选，和1个阳性位点进行筛选标记在平均密度为0.5 centimorgan，并进行参数连锁analysis.Results：在10个受影响的家庭成员，ARMD表现为存在大，软，融合性玻璃疣伴有不同程度的视网膜色素上皮变性和/或地图状萎缩。黄斑变性为常染色体显性遗传，其致病位点位于染色体1 q25-q31，位于D1 S466和D1 S413之间，多点lod值为3.00。结论：黄斑变性定位于染色体1 q25-q31（基因符号，ARMD 1）作为一个大家族的显性性状，主要表现为干性表型。临床相关性：ARMD基因的鉴定将有助于ARMD的早期诊断和分子病理生理机制的理解。这些知识将有助于制定预防和改进治疗战略。
Objectives: To identify the chromosomal location of a disease-causing gene and to describe the clinical characteristics of a large family with age-related macular degeneration (ARMD).Methods: An ARMD pedigree was identified, and the disease state of family members was documented by stereoscopic fundus photography and was classified using a modified version of the Wisconsin Age-Related Maculopathy Grading System. A genome-wide screen at approximately 6-centimorgan spacing using a DNA-pooling strategy combined with shared-segment analysis was used to identify likely chromosomal regions. The entire family was then screened at each likely locus, and 1 positive locus was refined by screening with markers at an average density of 0.5 centimorgan and subjected to parametric linkage analysis.Results: In the 10 affected family members, ARMD was manifest by the presence of large, soft, confluent drusen accompanied by varying degrees of retinal pigment epithelial degeneration and/or geographic atrophy. Age-related macular degeneration segregated as an autosomal-dominant trait, with the disease locus mapping to chromosome 1q25-q31 between markers D1S466 and D1S413, with a multipoint lod score of 3.00.Conclusion: Age-related macular degeneration localized to chromosome 1q25-q31 (gene symbol, ARMD1) as a dominant trait in a large family with a predominantly dry phenotype.Clinical Relevance: Identification of ARMD genes will facilitate early diagnosis and aid in understanding the molecular pathophysiological mechanisms of ARMD. This knowledge will contribute to the development of preventive and improved treatment strategies.