ABCMdb

PMID: 19578016

Genead MA, Fishman GA, Stone EM, Allikmets R
The natural history of stargardt disease with specific sequence mutation in the ABCA4 gene.
Invest Ophthalmol Vis Sci. 2009 Dec;50(12):5867-71. Epub 2009 Jul 2., [PubMed]

Sentences

No. Mutations Sentence Comment

1 ABCA4 p.Gly1961Glu To determine longitudinal changes in fundus appearance and visual function in patients with Stargardt with at least one allelic mutation (Gly1961Glu) in the ABCA4 gene. Login to comment 3 ABCA4 p.Gly1961Glu Sixteen patients with a diagnosis of Stargardt disease and a Gly1961Glu mutation were enrolled. Login to comment 11 ABCA4 p.Gly1961Glu In these patients with Stargardt disease and a Gly1961Glu mutation, most showed a clinical phenotype characterized by fundus changes localized to the foveal and parafoveal regions, normal ERG amplitudes, absence of a silent or masked choroid, and a mean age at initial presentation in the third decade. Login to comment 18 ABCA4 p.Gly1961Glu In a previous study by Fishman and et al.,12 an association was observed between a certain ABCA4 genotype, in which the amino acid glutamic acid is substituted for glycine (Gly1961Glu), and a Stargardt disease phenotype. Login to comment 21 ABCA4 p.Gly1961Glu In stage IV, there is extensive atrophy of the RPE and choroid.12 Eleven of the patients with Gly1961Glu mutations cited in Fishman et al.12 were also included in the current natural history study. Login to comment 22 ABCA4 p.Gly1961Glu The purpose of the present study was to determine longitudinal changes in visual acuity, fundus morphologic features, central scotoma size, and ERG amplitudes in patients with Stargardt with at least one allelic mutation (Gly1961Glu) in the ABCA4 gene. Login to comment 23 ABCA4 p.Gly1961Glu MATERIALS AND METHODS Patient Ascertainment One of the authors (GAF) referred 16 patients with a diagnosis of Stargardt macular dystrophy and a specific ABCA4 sequence mutation (Gly1961Glu) on at least one allele for the present study. Login to comment 52 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu RESULTS Of the 16 patients with Gly1961Glu mutations, 6 (37.5%) had the Gly1961Glu mutation on one allele (heterozygous), whereas 1 (6.2%) was homozygous for the mutation and 9 (56.2%) had a compound heterozygous mutation (Table 1). Login to comment 66 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro ABCA4 p.Pro1380Leu ABCA4 p.Pro1380Leu ABCA4 p.Leu1201Arg ABCA4 p.Arg2077Trp ABCA4 p.Gly65Glu Genetic Mutations in the ABCA4 Gene in the Patients Patient No. Genetic Mutation Allele 1 Genetic Mutation Allele 2 Comments 1 gly1961glu exon 42 Heterozygous 2 gly1961glu exon 42 ala1038val exon 21 and leu541pro exon 12 Compound heterozygous 3 gly1961glu exon 42 Heterozygous 4 gly1961glu exon 42 arg2077trp exon 45 Compound heterozygous 5 gly1961glu exon 42 gly65glu exon 3 Compound heterozygous 6 gly1961glu exon 42 leu1201arg exon 24 Compound heterozygous 7 gly1961glu exon 42 Heterozygous 8 gly1961glu exon 42 Heterozygous 9 gly1961glu exon 42 del Co 1620-1622 exon 35 Compound heterozygous 10 gly1961glu exon 42 Heterozygous 11 gly1961glu exon 42 1bp del(T) Co 36 which creates stop at Co 38 Compound heterozygous 12 gly1961glu exon 42 IVS38-10 TϾC Compound heterozygous 13 gly1961glu exon 42 Heterozygous 14 gly1961glu exon 42 pro1380leu Compound heterozygous 15 gly1961glu exon 42 pro1380leu Compound heterozygous 16 gly1961glu exon 42 gly1961glu exon 42 Homozygous initial visit in the right eye was 0.87 (range, 0.10-1.40), whereas the median logMAR VA at the most recent FU visit was 1.00 (range, 0.18-2.80; P ϭ 0.325). Login to comment 81 ABCA4 p.Gly1961Glu Follow-up Period in Stargardt Macular Dystrophy with Gly1961Glu Mutations Follow-up Period (y) Patients, n (%) 6-10 3 (18.8) 11-15 4 (25.0) b0e;15 9 (56.2) Total 16 (100) a III4e stimulus over a mean of 15.5 years (median, 15.5; range, 6 to 25 years; Table 7). Login to comment 82 ABCA4 p.Gly1961Glu Follow-up Period in Stargardt Macular Dystrophy with Gly1961Glu Mutations Follow-up Period (y) Patients, n (%) 6-10 3 (18.8) 11-15 4 (25.0) Ͼ15 9 (56.2) Total 16 (100) a III4e stimulus over a mean of 15.5 years (median, 15.5; range, 6 to 25 years; Table 7). Login to comment 87 ABCA4 p.Gly1961Glu DISCUSSION The present study, to our knowledge, is the first to demonstrate the natural history of structural and functional changes observed in the course of disease in patients with Stargardt disease and a Gly1961Glu sequence mutation in the ABCA4 gene. Login to comment 88 ABCA4 p.Gly1961Glu DISCUSSION The present study, to our knowledge, is the first to demonstrate the natural history of structural and functional changes observed in the course of disease in patients with Stargardt disease and a Gly1961Glu sequence mutation in the ABCA4 gene. Login to comment 90 ABCA4 p.Gly1961Glu In a previous report, Guymer et al.21 described that there was a significant difference in the frequency of the G1y1961Glu allele between visually normal individuals of Somali ancestry (11.3%) and visually normal individuals from a United States population (0.4%).This finding implies a potential for a higher prevalence of individuals who are homozygous for the Gly1961Glu mutation in the Somali population. Login to comment 91 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu In a previous report, Guymer et al.21 described that there was a significant difference in the frequency of the G1y1961Glu allele between visually normal individuals of Somali ancestry (11.3%) and visually normal individuals from a United States population (0.4%).This finding implies a potential for a higher prevalence of individuals who are homozygous for the Gly1961Glu mutation in the Somali population. Login to comment 92 ABCA4 p.Gly1961Glu In our group of patients with Stargardt disease and at least one Gly1961Glu mutation, visual acuity was eventually reduced to a level of 20/200 to 20/400. Login to comment 100 ABCA4 p.Gly1961Glu This finding is also consistent with observations of Fishman et al.,12 who showed that 90.0% (9/10) of patients with Stargardt with a Gly1961Glu mutation showed normal rod and cone ERG responses. Login to comment 101 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu This finding is also consistent with observations of Fishman et al.,12 who showed that 90.0% (9/10) of patients with Stargardt with a Gly1961Glu mutation showed normal rod and cone ERG responses. Login to comment 102 ABCA4 p.Gly1961Glu In our patients with Stargardt disease and a Gly1961Glu mutation, a high percentage initially presented and then maintained stage I disease; did not manifest a dark choroid; and as a group, maintained normal ERG cone and rod amplitudes. Login to comment