ABCMdb

PMID: 23882696

Ritter M, Zotter S, Schmidt WM, Bittner RE, Deak GG, Pircher M, Sacu S, Hitzenberger CK, Schmidt-Erfurth UM
Characterization of stargardt disease using polarization-sensitive optical coherence tomography and fundus autofluorescence imaging.
Invest Ophthalmol Vis Sci. 2013 Sep 27;54(9):6416-25. doi: 10.1167/iovs.12-11550., [PubMed]

Sentences

No. Mutations Sentence Comment

102 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Arg2107His ABCA4 p.Leu1580Ser ABCA4 p.Val931Met ABCA4 p.Thr1089Ile ABCA4 p.Glu955Gly ABCA4 p.Glu955Gly ABCA4 p.Met1209Thr Patient Characteristics Patient Number Sex Age Age of Onset Visual Acuity RE/LE Fundus Phenotype ERG Type ABCA4 Mutation Allele 1 ABCA4 Mutation Allele 2 Exon Position cDNA Effect on Protein Exon Position cDNA Effect on Protein 1 M 52 19 1.00/1.30 1 2 33 c.4738_4739delTT p.Leu1580Lysfs*16 46 c.6320G>A p.Arg2107His 2 F 32 9 1.30/1.00 1 1 19 c.2829delG p.Pro944Glnfs*6 42 c.5882G>A p.Gly1961Glu 3 M 29 16 1.30/1.00 1 1 IVS1 c.66&#fe;3A>C / 19 c.2791G>A p.Val931Met 4 F 32 20 1.00/1.00 1 1 17 c.2588G>C* p.Gly863Ala* 22 c.3266C>T p.Thr1089Ile 5 M 28 21 0.52/0.70 1 1 42 c.5882G>A p.Gly1961Glu 42 c.5882G>A p.Gly1961Glu 6 F 25 20 1.00/0.80 1 1 13 c.1865delG p.Ser622Thrfs*27 42 c.5882G>A p.Gly1961Glu 7 F 32 27 0.05/0.10 2 1 25 c.3626T>C p.Met1209Thr 33 c.4739T>C p.Leu1580Ser 8 F 42 17 1.00/1.00 2 1 12 c.1622T>C* p.Leu541Proߤ 42 c.5882G>A p.Gly1961Glu 9 F 23 23 0.00/0.00 2 1 IVS40 c.5714&#fe;5G>A / IVS40 c.5714&#fe;5G>A / 10 F 30 16 1.00/1.00 2 1 12 c.1622T>Cߤ p.Leu541Proߤ 19 c.2864A>G p.Glu955Gly 11 M 45 19 1.30/1.30 3 2 12 c.1622T>Cߤ p.Leu541Proߤ 17 c.2588G>C* p.Gly863Ala* 12 M 37 14 1.00/1.00 3 2 12 c.1622T>Cߤ p.Leu541Proߤ 19 c.2864A>G p.Glu955Gly 13 F 27 20 1.00/1.00 3 2 12 c.1622T>Cߤ p.Leu541Proߤ IVS40 c.5714&#fe;5G>A / 14 M 41 14 2.00/2.00 3 3 IVS13 c.1937&#fe;1G>A / 17 c.2588G>C* p.Gly863Ala* Patient number, sex, age, age of disease onset, visual acuity (logMAR), fundus phenotype (1, STGD phenotype 1; 2, STGD phenotype 2; 3, STGD phenotype 3), ERG type, ABCA4 mutation allele 1 and ABCA4 mutation allele 2; exons and coding DNA (cDNA) positions based on reference sequence NM_000350 (IVS: intervening sequence, intron) are shown. Login to comment 104 ABCA4 p.Arg943Glu * Linked to c.2828G>A (p.Arg943Glu). Login to comment 105 ABCA4 p.Ala1038Val ߤ Linked to c.3113C>T (p.Ala1038Val). Login to comment 109 ABCA4 p.Gly1961Glu ABCA4 p.Arg2107His ABCA4 p.Val931Met The four patients showing a central area of RPE atrophy were compound heterozygous for a known missense mutation and for a novel, previously not described, mutation: patient 1 harbored the known c.6320G>A (p.Arg2107His) mutation and a, so far not described, null mutation in exon 33, c.4738_4739delTT (p.Leu1580Lysfs*16), patient 2 the frequent mild missense mutation c.5882G>A (p.Gly1961Glu) and a novel single-base deletion, c.2829delG (p.Pro944Glnfs*6) in exon 19, and patient 3 the known c.2791G>A (p.Val931Met) mutation and a presumably destructive novel splice site mutation within the first intron (c.66&#fe;3A>C). Login to comment 111 ABCA4 p.Gly863Ala ABCA4 p.Arg943Gln ABCA4 p.Thr1089Ile [2588G>C; 2828G>A] (p.[Gly863Ala; Arg943Gln]) and a, so far unknown, missense mutation in exon 22, c.3266C>T (p.Thr1089Ile), which affects a highly conserved threonine residue within the transmembrane helix and is predicted to be deleterious. Login to comment 112 ABCA4 p.Gly1961Glu Both patients characterized by a foveal cavitation carried the frequent mild p.Gly1961Glu mutation, which was homozygous in patient 5 and compound heterozygous with a novel single-base deletion in exon 13, c.1865delG (p.Ser622Thrfs*27) in patient 6. Login to comment 123 ABCA4 p.Glu955Gly In one patient, a so far unknown missense mutation in exon 19 was detected, c.2864A>G (p.Glu955Gly), which affects a conserved residue within the ABC transporter 1 domain and is predictably pathogenic. Login to comment 143 ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro ABCA4 p.Glu955Gly [1622T>C; 3113C>T] (p.[Leu541Pro; Ala1038Val]), which is generally considered to be associated with more severe disease progression.40 Patient 12 carried this allele together with the same novel missense mutation (p.Glu955Gly) on the second chromosome as his younger sister (patient 10, STGD phenotype 2), which is suggestive of intrafamilial phenotype variation associated with this specific combination of ABCA4 mutations. Login to comment 197 ABCA4 p.Gly1961Glu ABCA4 p.Gly863Ala ABCA4 p.Arg943Glu [2588G>C; 2828G>A] p.[Gly863Ala; Arg943Glu]; II: c.5714&#fe;5G>A; III: c.5882G>A p.Gly1961Glu) or severe (c. Login to comment 198 ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro [1622T>C; 3113C>T p.[Leu541Pro; Ala1038Val]), respectively. Login to comment 201 ABCA4 p.Gly1961Glu Both patients with the foveal cavitation phenotype carried the mild Gly1961Glu mutation, either homozygous or in combination with a null mutation. Login to comment 202 ABCA4 p.Leu541Pro On the other hand, STGD phenotype 2 was associated with the presence of the known severe complex mutation Leu541Pro/ Ala10398Val in two of four cases, while three of four patients within phenotype 3 carried this mutation. Login to comment