Klein M L, Schultz D W, Edwards A, Matise T C, Rust K, Berselli C B, Trzupek K, Weleber R G, Ott J, Wirtz M K, Acott T S
Macular Degeneration Center, Casey Eye Institute, Oregon Health Sciences University, Portland, USA.
Arch Ophthalmol. 1998 Aug;116(8):1082-8. doi: 10.1001/archopht.116.8.1082.
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).
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.
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.
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.
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.
确定致病基因的染色体定位，并描述一个患有年龄相关性黄斑变性（ARMD）的大家族的临床特征。
确定一个ARMD家系，通过立体眼底摄影记录家庭成员的疾病状态，并使用威斯康星年龄相关性黄斑病变分级系统的改良版进行分类。采用DNA池策略结合共享片段分析，以约6厘摩的间距进行全基因组筛查，以确定可能的染色体区域。然后对整个家系在每个可能的位点进行筛查，通过平均密度为0.5厘摩的标记物进行筛查来精确定位1个阳性位点，并进行参数连锁分析。
在10名受影响的家庭成员中，ARMD表现为存在大的、软性的、融合性玻璃膜疣，并伴有不同程度的视网膜色素上皮变性和/或地图样萎缩。年龄相关性黄斑变性作为常染色体显性性状分离，疾病位点定位于标记物D1S466和D1S413之间的染色体1q25 - q31，多点对数计分法得分为3.00。
在一个以干性表型为主的大家族中，年龄相关性黄斑变性作为显性性状定位于染色体1q25 - q31（基因符号，ARMD1）。
鉴定ARMD基因将有助于早期诊断，并有助于理解ARMD的分子病理生理机制。这些知识将有助于制定预防和改进治疗策略。
