ABCMdb

PMID: 9466990

Cremers FP, van de Pol DJ, van Driel M, den Hollander AI, van Haren FJ, Knoers NV, Tijmes N, Bergen AA, Rohrschneider K, Blankenagel A, Pinckers AJ, Deutman AF, Hoyng CB
Autosomal recessive retinitis pigmentosa and cone-rod dystrophy caused by splice site mutations in the Stargardt's disease gene ABCR.
Hum Mol Genet. 1998 Mar;7(3):355-62., [PubMed]

Sentences

No. Mutations Sentence Comment

100 ABCA4 p.Gly863Ala The Gly863Ala mutation was found in another 20 of a total of 58 STGD patients, but not in 100 control individuals. Login to comment 101 ABCA4 p.Gly863Ala The Gly863Ala mutation thereby is one of the most frequently observed mutations in our STGD patient cohort. Login to comment 102 ABCA4 p.Gly863Ala The Gly863Ala mutation was found in another 20 of a total of 58 STGD patients, but not in 100 control individuals. Login to comment 103 ABCA4 p.Gly863Ala The Gly863Ala mutation thereby is one of the most frequently observed mutations in our STGD patient cohort. Login to comment 104 ABCA4 p.Ala1038Val STGD patient 8439 carries a CT transition at nucleotide position 3113, resulting in an Ala1038Val mutation in the predicted ABCR protein (Table 1). Login to comment 106 ABCA4 p.Ala1038Val ABCA4 p.Ala1028Val STGD patient 8439 carries a C!T transition at nucleotide position 3113, resulting in an Ala1038Val mutation in the predicted ABCR protein (Table 1). Login to comment 108 ABCA4 p.Ala1028Val This mutation was previously erroneously designated Ala1028Val (18; R.Allikmets, personal communication). Login to comment 123 ABCA4 p.Gly863Ala If the cryptic 5' splice site is used there will be a 10 amino acid insertion after amino acid position 1513 (in ref. 18, amino acid position 1475) of the predicted ABCR protein (Fig. 5, splice variantB).TheIVS30+1G࢐Tmutationwasalsoobservedintwo STGD patients, one of which carried a Gly863Ala mutation in the second allele. Login to comment 125 ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala Genotype-phenotype comparison for the RP, CRD, STGD/FFM and AMD patients and a hypothetical correlation between ABCR activity and the observed phenotypes Patient Phenotype ABCR allele 1 ABCR allele 2 ABCR activity 7023 (V-3) RP IVS30+1G࢐T IVS30+1G࢐T - 7028 (IV-7) CRD IVS30+1G࢐T IVS40+5G࢐A +/- 7560 STGD IVS30+1G࢐T Gly863Ala + 7727 STGD IVS30+1G࢐T Unknown + 8439 STGD IVS40+5G࢐A Ala1038Val + 8272 STGD/FFM IVS40+5G࢐A Unknown + AMD Missense or null mutation (19) ++ Normal ++++ Figure 5. Login to comment 126 ABCA4 p.Gly863Ala 18, amino acid position 1475) of the predicted ABCR protein (Fig. 5, splice variantB).TheIVS30+1G→Tmutationwasalsoobservedintwo STGD patients, one of which carried a Gly863Ala mutation in the second allele. Login to comment 128 ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala Genotype-phenotype comparison for the RP, CRD, STGD/FFM and AMD patients and a hypothetical correlation between ABCR activity and the observed phenotypes Patient Phenotype ABCR allele 1 ABCR allele 2 ABCR activity 7023 (V-3) RP IVS30+1G→T IVS30+1G→T - 7028 (IV-7) CRD IVS30+1G→T IVS40+5G→A +/- 7560 STGD IVS30+1G→T Gly863Ala + 7727 STGD IVS30+1G→T Unknown + 8439 STGD IVS40+5G→A Ala1038Val + 8272 STGD/FFM IVS40+5G→A Unknown + AMD Missense or null mutation (19) ++ Normal ++++ 3360 Figure . Login to comment 136 ABCA4 p.Gly863Ala Given the more severe clinical picture in RP patients compared with CRD and STGD patients, it can be deduced that homozygosity for the IVS30+1G࢐T mutation, associated with an RP phenotype, is more detrimental to ABCR activity than compound heterozygosity for the IVS30+1G࢐T and IVS40+5G࢐A mutations, which results in a CRD phenotype, or compound heterozygosity for the IVS30+1G࢐T and Gly863Ala mutations, which results in an STGD phenotype. Login to comment 139 ABCA4 p.Gly863Ala Given the more severe clinical picture in RP patients compared with CRD and STGD patients, it can be deduced that homozygosity for the IVS30+1G→T mutation, associated with an RP phenotype, is more detrimental to ABCR activity than compound heterozygosity for the IVS30+1G→T and IVS40+5G→A mutations, which results in a CRD phenotype, or compound heterozygosity for the IVS30+1G→T and Gly863Ala mutations, which results in an STGD phenotype. Login to comment