ABCMdb

PMID: 10206579

Fishman GA, Stone EM, Grover S, Derlacki DJ, Haines HL, Hockey RR
Variation of clinical expression in patients with Stargardt dystrophy and sequence variations in the ABCR gene.
Arch Ophthalmol. 1999 Apr;117(4):504-10., [PubMed]

Sentences

No. Mutations Sentence Comment

6 ABCA4 p.Gly1961Glu In phenotype I, 9 of 12 patients had a sequence change in exon 42 of the ABCR gene in which the amino acid glutamic acid was substituted for glycine (Gly1961Glu). Login to comment 10 ABCA4 p.Gly1961Glu None exhibited the Gly1961Glu change. Login to comment 13 ABCA4 p.Gly1961Glu One patient showed the Gly1961Glu change. Login to comment 15 ABCA4 p.Gly1961Glu In individual patients, a certain phenotype seems to be associated with the presence of a Gly1961Glu change in exon 42 of the ABCR gene. Login to comment 31 ABCA4 p.Gly1961Glu These patients would have been classified as having stage 1 disease as described by Fishman.14 Of interest, 9 of the 12 patients showed a Gly1961Glu sequence variation on 1 allele of the ABCR gene (Table 1), none of whom showed a dark choroid or abnormal ERG findings. Login to comment 66 ABCA4 p.Gly1961Glu Such patients were previously categorized as having stage 3 or stage 4 disease.14 One of the 7 patients in this subgroup showed a compound heterozygous sequence variation in which 1 allele had a Gly1961Glu change. Login to comment 70 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.Ala1038Val ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Arg2107His ABCA4 p.Arg2107His ABCA4 p.Arg2107His ABCA4 p.Arg2107His ABCA4 p.Cys1488Arg ABCA4 p.Arg2038Trp ABCA4 p.Arg1108Cys ABCA4 p.Cys2150Tyr ABCA4 p.Arg2077Trp ABCA4 p.Trp1408Leu ABCA4 p.Thr300Asn ABCA4 p.Gly65Glu ABCA4 p.Val849Ala ABCA4 p.Val849Ala ABCA4 p.Ala60Val ABCA4 p.Ser206Arg ABCA4 p.His2128Arg ABCA4 p.Tyr1652Asp ABCA4 p.Leu1729Pro ABCA4 p.Ser974Pro Clinical Features of Patients With ABCR Gene Mutations* Patient No./ Sex/Age, y Clinical Phenotype Vision Silent Choroid Central Scotoma MutationOD OS 1/M/19 I 20/200 20/200 ND + Thr300Asn, exon 8 2/M/44 I 20/25 20/15 - + Cys1488Arg, exon 30 3/M/35 I 20/100 20/100 ND + Gly1961Glu, exon 42 Cys2150Tyr, exon 47 4/M/44 I 20/200 20/200 - + Gly1961Glu, exon 42 5/F/28 I 20/80 20/100 - + Gly1961Glu, exon 42 Gly65Glu, exon 3 6/M/36 I 20/25 20/200 - + Gly1961Glu, exon 42 Arg2077Trp, exon 45 7/F/44 I 20/200 20/200 - + Gly1961Glu, exon 42 8/M/41 I 20/200 20/200 - + Gly1961Glu, exon 42 9/F/32 I 20/25 20/30 - + Gly1961Glu, exon 42 10/F/36 I 20/50 20/200 - + Gly1961Glu, exon 42 11/M/31 I 20/200 20/200 - + Gly1961Glu, exon 42 Ala1038Val, exon 21 Leu541Pro, exon 12 12/M/35 I 20/200 20/200 - + Arg2107His, exon 46 Leu1729Pro, exon 36 13/M/22 II 20/200 20/200 + + 1bp del (g), codon 448, exon 10 14/F/9 II 20/200 20/40 ND + 9bp del, codon 1760/1761, exon 37 1bp ins (c), codon 1513, exon 30 15/M/19 II 10/120 10/160 + + 1bp ins (c), codon 1513, exon 30 Ala60Val, exon 3 16/M/25 II 20/200 20/200 + ND Ser974Pro, exon 20 17/F/12 II 20/200 20/200 ND + 2884 del (c), exon 19 18/F/73 II 20/30 20/25 + Paracentral scotoma 5bp del, codon 505, exon 11 19/F/35 II 10/160 10/120 ND + Val849Ala, exon 16 20/F/48 II 20/400 20/400 + +; Mild peripheral restriction Val849Ala, exon 16 Arg2107His, exon 46 21/M/54 II 20/200 20/200 + + Arg2030stop, exon 44 22/M/28 II 20/400 20/400 + + His2128Arg, exon 46 23/F/34 III 10/400 10/225 Diffuse hyperfluorescence ND Arg2038Trp, exon 44 24/F/53 III 10/700 10/600 Diffuse hyperfluorescence and notable choroidal atrophy + Arg1108Cys, exon 22 25/F/54 III 10/350 3/350 Diffuse hyperfluorescence +; Mild concentric restriction Tyr1652Asp, exon 35 Arg2107His, exon 46 26/M/57 III 20/50 20/80 ND ND Splice donor GϾA, exon 24 27/F/65 III 1/225 1/225 Diffuse choroidal atrophy Temporal islands Gly1961Glu, exon 42 frameshift del, codons 1620-1622, exon 35† 28/M/32 III 20/400 20/400 Diffuse hyperfluorescence +; Peripheral restriction Ala1038Val, exon 21 Leu541Pro, exon 12 Donor splice, exon 30 29/M/46 III 10/225 10/225 ND +; Peripheral restriction Trp1408Leu, exon 28 Ser206Arg, exon 6 Arg2107His, exon 46 *M indicates male; F, female; ND, angiography or visual field testing not done; +, present; and -, absent. Login to comment 90 ABCA4 p.Gly1961Glu With 1 exception, the Gly1961Glu sequence variation was observed in patients with a phenotype I expression. Login to comment 99 ABCA4 p.Gly1961Glu For example, suppose that the Gly1961Glu change is in fact a non-disease-causing polymorphism present in a relatively small portion of the general population. Login to comment 100 ABCA4 p.Gly1961Glu If a true disease-causing mutation occurred by chance in the promoter region of such a "1961- marked" allele, then one would expect an enrichment of the Gly1961Glu sequence change among a group of patients with Stargardt dystrophy (compared with the Figure 7. Login to comment 106 ABCA4 p.Gly1961Glu However, even if such an event were to occur, clinical associations with the marker polymorphism (such as the association between the Gly1961Glu sequence change and phenotype I in this article) would be meaningful only as long as the frequency of the polymorphism in the general population was relatively low. 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