Mutation of the Stargardt Disease Gene (ABCR) in Age-related Macular Degeneration

Abstract

mmm appear to contain cloning artifacts. 13. The 5' end of the human cDNA was obtained by two rounds of PCR amplification of the CLN2 candidate from a human cortex cDNA library (Stratagene) by means of two different gene-specific primers and a single vector-specific primer. In the first round of PCR the T3 promoter primer was used with either gene-specific primer NR1 (5'-GT-GATCACAGAATGGCACTT) or NR2 (5'-AACAT-GGGTTTCCGTAGGTC). In the second round of PCR, with the products from the first amplification, the T3 promoter primer and NR4 (5'-CTTCCT-CAGGGTCCGCACGG) were used. 14. GenBank accession number AF017456. 15. Three lines of evidence give corroborative results for an unequivocal localization, (i) There is a nearly perfect match between nt 34 to 104 of the CLN2 cDNA candidate and GenBank accession number B04497, which represents a PCR-amplified fragment of a-flow-sorted chromosome 11-specific cosmid clone. (The 317-nt B04497 also contains sequence of flanking introns.) (ii) There is a perfect 505-nt match between the 3' end of the CLN2 cDNA (nt 2979 to 3483) and the 5' end (nt 1 to 505) of GenBank accession number U25816. U25816 consists of 2605 nt that encompass the human TATAbinding protein associated factor II 30 (TAFn30) gene. The TAFM30 transcription start site is at U25816 nt 1060, and most of the promoter elements are downstream of U25816 nt 860 and thus do not overlap with the 3' end of the large CLN2 candidate transcript. Thus, the CLN2 candidate gene and the TAFn30 gene are physically adjacent. The TAF,|30 gene was mapped to chromosome 11 p15.2-p15.5 by means of in situ hybridization [E.

Retinal Histopathology in Eyes from a Patient with Stargardt disease caused by Compound Heterozygous ABCA4 Mutations

“…12,[14][15][16][17][18][19] It is the most common mutation detected in ABCA4 with a frequency that varies from approximately 0.2% in Europeans 20,21 to approximately 10% in East African populations. 14,22,23 In addition, this mutation has also been identified in patients with autosomal recessive cone-rod dystrophy 2,24,25 and age-related macular degeneration.…”

“…14,22,23 In addition, this mutation has also been identified in patients with autosomal recessive cone-rod dystrophy 2,24,25 and age-related macular degeneration. 12,18,26 A recent report classified the severity of phenotypes in individuals carrying homozygous p.Gly1961Glu mutations as mild to moderate based on clinical characteristics including: age of onset; the minimum angle of visual acuity resolution; fundus appearance; autofluorescence pattern; and ERG characteristics. 15,16 Additional reports also indicate that patients homozygous for this mutation usually have a milder form of the disease, with more severe phenotypes linked to the presence of a third or fourth ABCA4 mutation.…”

“…Within the RPE the all-trans retinal is converted to A2-E, a major component of lipofuscin, which is thought to be toxic to both the RPE and the photoreceptors. 12,13 It is not known whether the ultimate loss of vision in patients with STGD occurs primarily from dysfunction of the RPE, photoreceptors, or both.…”

Association of CFH Y402H Polymorphism with Both Forms of Advanced Age-Related Macular Degeneration in Turkish Patients

“…Family-based studies, especially the ones on twin studies, and population-based studies showed the association between some gene variants and AMD. [10][11][12][13][14] The gene variants related to AMD are: CFH, [16][17][18][19][20] LOC387715, 21 HTRA1, 22 ABCA4, 23 APOE, 24 FBLN5 25 and ELOVL4. 26 Among these, the first three variants are found to be strongly associated with AMD.…”

Multiple Drug Resistance Associated with Function of ABC-Transporters in Diabetes Mellitus: Molecular Mechanism and Clinical Relevance

“…Lung surfractant deficiency causing fatal neonatal respiratory distress can be caused by mutations in ABCA3 [45], while mutations in the retina-specific ABCA4 have been associated with Stargardt disease [46], and many other retinal defects. Mutations in ABCA1 have been shown to cause Tangier Disease, a rare autosomal recessive disorder of lipid metabolism [47,48,49].…”