Analysis of the stargardt disease gene (ABCR) in age-related macular degeneration☆

Paz, Monica A. De La; Guy, Vanessa K.; Abou-Donia, Suzanne M.; Heinis, Ruth; Bracken, Bekki; Vance, Jeffery M.; Gilbert, John R.; Gass, J. Donald M.; Haines, Jonathan L.; Pericak‐Vance, Margaret A.

doi:10.1016/s0161-6420(99)90449-9

Cited by 86 publications

(40 citation statements)

References 31 publications

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“…They did, however, find that the two ABCA4 variant alleles were slightly more frequent in patients with the exudative form (or wet-type) of AMD versus those without this complication (2.7% compared to 2.5%, respectively) . De La Paz et al (1999)observed rates of ABCA4 variants significantly lower (1.2%) than the rates Allikmets et al reported (16%, p =0.00001; see above). Furthermore, the D2177N variant was only reported in two AMD sporadic individuals and this allele was not found in any of the familial AMD cases in this study.…”

Section: Amd-related Snps In Genes Associated With Monogenic Macular mentioning

confidence: 51%

“…Furthermore, the D2177N variant was only reported in two AMD sporadic individuals and this allele was not found in any of the familial AMD cases in this study. Interestingly, De La Paz et al (1999)did report that a newly identified polymorphism, T190A, was found among all affected members of one of their larger AMD families although it failed to definitively segregate with the disease phenotype in another family. Similarly, several other independent reports found no evidence for significant association or cosegregation with the disease in family-based studies Schmidt et al, 2003;Souied et al, 2000;Stone et al, 1998;Webster et al, 2001).…”

Section: Amd-related Snps In Genes Associated With Monogenic Macular mentioning

confidence: 99%

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Genetic factors of age-related macular degeneration

Tuo

Bojanowski

Chan

2004

Progress in Retinal and Eye Research

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Age-related macular degeneration (AMD) is a leading cause of blindness in the United States and developed countries. Although the etiology and pathogenesis of AMD remain unknown, a complex interaction of genetic and environmental factors is thought to exist. The incidence and progression of all of the features of AMD are known to increase significantly with age. The tendency for familial aggregation and the findings of gene variation association studies implicate a significant genetic component in the development of AMD. This review summarizes in detail the AMD-related genes identified by studies on genetically engineered and spontaneously gene-mutated (naturally mutated) animals, AMD chromosomal loci identified by linkage studies, AMD-related genes identified through studies of monogenic degenerative retinal diseases, and AMD-related gene variation identified by association studies.

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Section: Amd-related Snps In Genes Associated With Monogenic Macular mentioning

confidence: 51%

Section: Amd-related Snps In Genes Associated With Monogenic Macular mentioning

confidence: 99%

Genetic factors of age-related macular degeneration

Tuo

Bojanowski

Chan

2004

Progress in Retinal and Eye Research

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“…[8][9][10]40,41 In light of the present findings, this could be explained partially by a random inclusion or exclusion of GPS[+] patients in the respective study group and would be true particularly if the spectrum of AMD cases in these studies focused mainly on patients with GA, exudative changes or a balanced mixture of these two most frequent late-stage outcomes. For example, the initial study by Allikmets et al associated ABCA4 alterations mostly with the GA phenotype, where ABCA4 variants were found in 26 out of 134 patients.…”

Section: Discussionmentioning

confidence: 82%

A Subgroup of Age-Related Macular Degeneration is Associated With Mono-Allelic Sequence Variants in theABCA4Gene

Fritsche

Fleckenstein

Fiebig

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Age-related macular degeneration (AMD) is a heterogeneous condition of high prevalence and complex etiology involving genetic as well as environmental factors. By fundus autofluorescence (FAF) imaging, AMD can be classified into several distinct phenotypes, with one subgroup characterized by fine granular pattern with peripheral punctate spots (GPS [+]). Some features of GPS[+] overlap with Stargardt disease (STGD1), a recessive macular dystrophy caused by biallelic sequence variants in the ATP-binding cassette transporter 4 (ABCA4) gene. The aim of this study was to investigate the role of ABCA4 in GPS [+].METHODS. The ABCA4 gene was sequenced in 25 patients with the GPS[+] phenotype and 29 with geographic atrophy (GA)-AMD but no signs of GPS (GPS [-]). In addition, frequencies of risk-increasing alleles at three known AMD susceptibility loci, including complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), and complement component 3 (C3), were evaluated. RESULTS.We demonstrate that GPS[+] is associated significantly with monoallelic ABCA4 sequence variants. Moreover, frequencies of AMD risk-increasing alleles at CFH, ARMS2, and C3 are similar in GPS[+] and STGD1 patients, with risk allele frequencies in both subcategories comparable to populationbased control individuals estimated from 3,510 individuals from the NHLBI Exome Sequencing Project.CONCLUSIONS. Our data suggest that the GPS[+] phenotype is accounted for by monoallelic variants in ABCA4 and unlikely by the well-established AMD risk-increasing alleles at CFH, ARMS2, and C3. These findings provide support for a complex role of ABCA4 in the etiology of a minor proportion of patients with AMD. (Invest Ophthalmol Vis Sci.

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“…In analogy with PXE mutations in MRP6, the mutations in MRP2 consist of large deletions, splice site mutations, and͞or missense substitutions affecting the NBF. In addition to Dubin-Johnson syndrome, a number of recessive diseases are caused by mutations in other ABC transporter genes, including cystic fibrosis and the Stargardt disease (25)(26)(27)(28).…”

Section: Discussionmentioning

confidence: 99%

Pseudoxanthoma elasticum: Mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter

Ringpfeil

Lebwohl

Christiano

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

361

252

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Pseudoxanthoma elasticum (PXE), the prototypic heritable connective tissue disorder affecting the elastic structures in the body, manifests with cutaneous, ophthalmologic, and cardiovascular findings, with considerable morbidity and mortality. The molecular basis of PXE has remained unknown, but the disease locus has recently been mapped to an Ϸ500-kb interval on chromosome 16p13.1, without evidence for locus heterogeneity. In this study, we report pathogenetic mutations in MRP6, a member of the ABC transporter gene family, in eight kindreds with PXE. The mutation detection strategy consisted of heteroduplex scanning of coding sequences in the MRP6 gene, which were amplified by PCR by using genomic DNA as template, followed by direct nucleotide sequencing. A total of 13 mutant MRP6 alleles were disclosed in the eight probands with PXE. These genetic lesions consisted of either single base pair substitutions resulting in missense, nonsense, or splice site mutations, or large deletions resulting in allelic loss of the MRP6 locus. Examination of clinically unaffected family members in four multiplex families identified heterozygous carriers, consistent with an autosomal recessive inheritance pattern. Collectively, identification of mutations in the MRP6 gene provides the basis to examine the pathomechanisms of PXE and allows development of DNA-based carrier detection, prenatal testing, and preimplantation genetic diagnosis in families with a history of this disease.

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Analysis of the stargardt disease gene (ABCR) in age-related macular degeneration☆

Cited by 86 publications

References 31 publications

Genetic factors of age-related macular degeneration

Genetic factors of age-related macular degeneration

A Subgroup of Age-Related Macular Degeneration is Associated With Mono-Allelic Sequence Variants in theABCA4Gene

Pseudoxanthoma elasticum: Mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter

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