This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (101)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Aging/ Geriatrics  • Macular Degeneration  • Alert me on articles by topic  Social Bookmarking   What's this?

Clinical Features in a Large Family and Linkage to Chromosome 1q

Michael L. Klein, MD; Dennis W. Schultz, PhD; Al Edwards, MD, PhD; Tara C. Matise, PhD; Kristal Rust; C. Blair Berselli; Karmen Trzupek; Richard G. Weleber, MD; Jurg Ott, PhD; Mary K. Wirtz, PhD; Ted S. Acott, PhD

Arch Ophthalmol. 1998;116:1082-1088.

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.

From the Macular Degeneration Center, Casey Eye Institute, Oregon Health Sciences University, Portland (Drs Klein, Schultz, Edwards, Weleber, Wirtz, and Acott, Mss Rust and Trzupek, and Mr Berselli), and the Laboratory of Statistical Genetics, The Rockefeller University, New York, NY (Drs Matise and Ott).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

ARMS2 Is a Constituent of the Extracellular Matrix Providing a Link between Familial and Sporadic Age-Related Macular Degenerations
Kortvely et al.
IOVS 2010;51:79-88.
ABSTRACT | FULL TEXT  

Contribution of Copy Number Variation in the Regulation of Complement Activation Locus to Development of Age-Related Macular Degeneration
Schmid-Kubista et al.
IOVS 2009;50:5070-5079.
ABSTRACT | FULL TEXT  

Complement Component 3 (C3) Haplotypes and Risk of Advanced Age-Related Macular Degeneration
Park et al.
IOVS 2009;50:3386-3393.
ABSTRACT | FULL TEXT  

Genotype-Phenotype Correlations for Exudative Age-Related Macular Degeneration Associated with Homozygous HTRA1 and CFH Genotypes
Leveziel et al.
IOVS 2008;49:3090-3094.
ABSTRACT | FULL TEXT  

Toll-like Receptor Polymorphisms and Age-Related Macular Degeneration
Edwards et al.
IOVS 2008;49:1652-1659.
ABSTRACT | FULL TEXT  

Genetic susceptibility to age-related macular degeneration: a paradigm for dissecting complex disease traits
Swaroop et al.
Hum Mol Genet 2007;16:R174-R182.
ABSTRACT | FULL TEXT  

Contributions of Genetics to Our Understanding of Inherited Monogenic Retinal Diseases and Age-Related Macular Degeneration
Bok
Arch Ophthalmol 2007;125:160-164.
ABSTRACT | FULL TEXT  

The Quest for Genes Causing Complex Traits in Ocular Medicine: Successes, Interpretations, and Challenges
Iyengar
Arch Ophthalmol 2007;125:11-18.
ABSTRACT | FULL TEXT  

Retinal Pigment Epithelial Cells Synthesize Laminins, Including Laminin 5, and Adhere to Them through {alpha}3- and {alpha}6-Containing Integrins
Aisenbrey et al.
IOVS 2006;47:5537-5544.
ABSTRACT | FULL TEXT  

CFH, ELOVL4, PLEKHA1 and LOC387715 genes and susceptibility to age-related maculopathy: AREDS and CHS cohorts and meta-analyses
Conley et al.
Hum Mol Genet 2006;15:3206-3218.
ABSTRACT | FULL TEXT  

Association between Apolipoprotein E Polymorphisms and Age-related Macular Degeneration: A HuGE Review and Meta-Analysis
Thakkinstian et al.
Am J Epidemiol 2006;164:813-822.
ABSTRACT | FULL TEXT  

Analysis of the Y402H Variant of the Complement Factor H Gene in Age-Related Macular Degeneration.
Baird et al.
IOVS 2006;47:4194-4198.
ABSTRACT | FULL TEXT  

Systematic review and meta-analysis of the association between complementary factor H Y402H polymorphisms and age-related macular degeneration
Thakkinstian et al.
Hum Mol Genet 2006;15:2784-2790.
ABSTRACT | FULL TEXT  

Polymorphism p.402Y>H in the complement factor H protein is a risk factor for age related macular degeneration in an Italian population
Simonelli et al.
Br J Ophthalmol 2006;90:1142-1145.
ABSTRACT | FULL TEXT  

Association of the Y402H Polymorphism in Complement Factor H Gene and Neovascular Age-Related Macular Degeneration in Chinese Patients.
Lau et al.
IOVS 2006;47:3242-3246.
ABSTRACT | FULL TEXT  

Complement factor H polymorphism, complement activators, and risk of age-related macular degeneration.
Despriet et al.
JAMA 2006;296:301-309.
ABSTRACT | FULL TEXT  

Synergic effect of polymorphisms in ERCC6 5' flanking region and complement factor H on age-related macular degeneration predisposition
Tuo et al.
Proc. Natl. Acad. Sci. USA 2006;103:9256-9261.
ABSTRACT | FULL TEXT  

Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk
Rivera et al.
Hum Mol Genet 2005;14:3227-3236.
ABSTRACT | FULL TEXT  

Late-Onset Macular Degeneration and Long Anterior Lens Zonules Result from a CTRP5 Gene Mutation
Ayyagari et al.
IOVS 2005;46:3363-3371.
ABSTRACT | FULL TEXT  

Meta-analysis of genome scans of age-related macular degeneration
Fisher et al.
Hum Mol Genet 2005;14:2257-2264.
ABSTRACT | FULL TEXT  

Candidate gene analysis suggests a role for fatty acid biosynthesis and regulation of the complement system in the etiology of age-related maculopathy
Conley et al.
Hum Mol Genet 2005;14:1991-2002.
ABSTRACT | FULL TEXT  

Toll-like receptor 4 variant D299G is associated with susceptibility to age-related macular degeneration
Zareparsi et al.
Hum Mol Genet 2005;14:1449-1455.
ABSTRACT | FULL TEXT  

From The Cover: A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration
Hageman et al.
Proc. Natl. Acad. Sci. USA 2005;102:7227-7232.
ABSTRACT | FULL TEXT  

Association of HLA Class I and Class II Polymorphisms with Age-Related Macular Degeneration
Goverdhan et al.
IOVS 2005;46:1726-1734.
ABSTRACT | FULL TEXT  

Complement Factor H Polymorphism and Age-Related Macular Degeneration
Edwards et al.
Science 2005;308:421-424.
ABSTRACT | FULL TEXT  

Association of Apolipoprotein E Alleles with Susceptibility to Age-Related Macular Degeneration in a Large Cohort from a Single Center
Zareparsi et al.
IOVS 2004;45:1306-1310.
ABSTRACT | FULL TEXT  

Analysis of the ARMD1 locus: evidence that a mutation in HEMICENTIN-1 is associated with age-related macular degeneration in a large family
Schultz et al.
Hum Mol Genet 2003;12:3315-3323.
ABSTRACT | FULL TEXT  

The genetics of inherited macular dystrophies
Michaelides et al.
J. Med. Genet. 2003;40:641-650.
ABSTRACT | FULL TEXT  

Late-Onset Autosomal Dominant Macular Dystrophy with Choroidal Neovascularization and Nonexudative Maculopathy Associated with Mutation in the RDS Gene
Khani et al.
IOVS 2003;44:3570-3577.
ABSTRACT | FULL TEXT  

A Strong and Highly Significant QTL on Chromosome 6 that Protects the Mouse from Age-Related Retinal Degeneration
Danciger et al.
IOVS 2003;44:2442-2449.
ABSTRACT | FULL TEXT  

Lack of an Association of Apolipoprotein E Gene Polymorphisms With Familial Age-Related Macular Degeneration
Schultz et al.
Arch Ophthalmol 2003;121:679-683.
ABSTRACT | FULL TEXT  

An Autosomal Dominant Bull's-Eye Macular Dystrophy (MCDR2) that Maps to the Short Arm of Chromosome 4
Michaelides et al.
IOVS 2003;44:1657-1662.
ABSTRACT | FULL TEXT  

The Prevalence of Age-Related Maculopathy in Iceland: Reykjavik Eye Study
Jonasson et al.
Arch Ophthalmol 2003;121:379-385.
ABSTRACT | FULL TEXT  

Shape Discrimination in Age-Related Macular Degeneration
Wang et al.
IOVS 2002;43:2055-2062.
ABSTRACT | FULL TEXT  

Genotype-Phenotype Analysis of ABCR Variants in Macular Degeneration Probands and Siblings
Bernstein et al.
IOVS 2002;43:466-473.
ABSTRACT | FULL TEXT  

Organization of the Human IMPG2 Gene and Its Evaluation as a Candidate Gene in Age-Related Macular Degeneration and Other Retinal Degenerative Disorders
Kuehn et al.
IOVS 2001;42:3123-3129.
ABSTRACT | FULL TEXT  

Cosegregation and functional analysis of mutant ABCR (ABCA4) alleles in families that manifest both Stargardt disease and age-related macular degeneration
Shroyer et al.
Hum Mol Genet 2001;10:2671-2678.
ABSTRACT | FULL TEXT  

Molecular genetics of age-related macular degeneration
Stone et al.
Hum Mol Genet 2001;10:2285-2292.
ABSTRACT | FULL TEXT  

Risk Factors for Age-Related Maculopathy: The Visual Impairment Project
McCarty et al.
Arch Ophthalmol 2001;119:1455-1462.
ABSTRACT | FULL TEXT  

Molecular genetic heterogeneity in autosomal dominant drusen
Tarttelin et al.
J. Med. Genet. 2001;38:381-384.
ABSTRACT | FULL TEXT  

Isolation of a Novel Iris-Specific and Leucine-Rich Repeat Protein (Oculoglycan) Using Differential Selection
Friedman et al.
IOVS 2000;41:2059-2066.
ABSTRACT | FULL TEXT  

A full genome scan for age-related maculopathy
Weeks et al.
Hum Mol Genet 2000;9:1329-1349.
ABSTRACT | FULL TEXT  

Genetic susceptibility to age related macular degeneration
Yates and Moore
J. Med. Genet. 2000;37:83-87.
ABSTRACT | FULL TEXT  

ABCR Gene Analysis in Familial Exudative Age-Related Macular Degeneration
Souied et al.
IOVS 2000;41:244-247.
ABSTRACT | FULL TEXT  

Autosomal Dominant Hemorrhagic Macular Dystrophy Not Associated With the TIMP3 Gene
Ayyagari et al.
Arch Ophthalmol 2000;118:85-92.
ABSTRACT | FULL TEXT  

Identifying genes that cause disease: HLA-B27, the paradigm, the promise, the perplexity
MARTIN and ROSENBAUM
Br J Ophthalmol 1998;82:1354-1355.
FULL TEXT