ABCMdb

ABCA4 p.Thr1253Met

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Publications

PMID: 22661473 [PubMed] Burke TR et al: "Retinal phenotypes in patients homozygous for the G1961E mutation in the ABCA4 gene."

No. Sentence Comment

89 Patient 3 had an additional heterozygous T1253M variant. Login to comment
91 Summary of Demographic, Clinical, and Functional Data in Patients Homozygous for the G1961E Mutation Patient #, Sex Additional ABCA4 Mutations Onset Age (years) Age at Exam (years) Duration (years) VA Clinical Phenotype ERG Group Silent Choroid Type of Perimetry Scotoma Location OD OS Milder Phenotypes 1, M 19 34 15 20/150 20/100 I I ND MP-1 Central 2, F 20 21 1 20/25 20/40 I I Absent ND ND 3, M T1253M 32 46 14 20/25 20/40 I I Absent GVF Perifoveal 4, F 43 67 24 20/40 20/150 II I ND MP-1 Central 5, F 48 65 17 20/150 20/200 I I ND MP-1 Central 6, F 64 86 22 20/200 20/200 II I Absent GVF Central Severe Phenotypes 7-1, M H1838D (Hom) 4 12 8 20/250 20/250 III III ND GVF Central 7-2, F H1838D (Hom) 7 13 6 20/200 20/200 IV III Peripapillary Ring GVF Central 8-1, F N96K 7 46 39 20/2000 20/2000 III III Peripapillary Ring GVF Central 8-2, M N96K 10 49 39 20/400 20/400 IV ND ND GVF Central 9, F N96K (Hom) 12 59 47 10/400 10/400 IV III ND ND ND 10, M 20 51 31 20/25 20/25 III RP ND GVF Perifoveal Each number identifies distinct families. Login to comment
106 Only one patient in this group (patient 3) had a heterozygous T1253M variant detected in the ABCA4 gene, in addition to the homozygous G1961E mutation. Login to comment
167 Six patients had other ABCA4 variants on the same chromosome with G1961E. Login to comment
168 One patient harbored a heterozygous T1253M variant, which previously has been reported sometimes to form a complex allele with G1961E.41 It is predicted to give rise to an amino acid change that lies outside the functional domain of the ABCA4 protein, it never occurs without G1961E, and, therefore, its pathogenicity has not been confirmed. Login to comment
88 Patient 3 had an additional heterozygous T1253M variant. Login to comment
90 Summary of Demographic, Clinical, and Functional Data in Patients Homozygous for the G1961E Mutation Patient #, Sex Additional ABCA4 Mutations Onset Age (years) Age at Exam (years) Duration (years) VA Clinical Phenotype ERG Group Silent Choroid Type of Perimetry Scotoma Location OD OS Milder Phenotypes 1, M 19 34 15 20/150 20/100 I I ND MP-1 Central 2, F 20 21 1 20/25 20/40 I I Absent ND ND 3, M T1253M 32 46 14 20/25 20/40 I I Absent GVF Perifoveal 4, F 43 67 24 20/40 20/150 II I ND MP-1 Central 5, F 48 65 17 20/150 20/200 I I ND MP-1 Central 6, F 64 86 22 20/200 20/200 II I Absent GVF Central Severe Phenotypes 7-1, M H1838D (Hom) 4 12 8 20/250 20/250 III III ND GVF Central 7-2, F H1838D (Hom) 7 13 6 20/200 20/200 IV III Peripapillary Ring GVF Central 8-1, F N96K 7 46 39 20/2000 20/2000 III III Peripapillary Ring GVF Central 8-2, M N96K 10 49 39 20/400 20/400 IV ND ND GVF Central 9, F N96K (Hom) 12 59 47 10/400 10/400 IV III ND ND ND 10, M 20 51 31 20/25 20/25 III RP ND GVF Perifoveal Each number identifies distinct families. Login to comment
105 Only one patient in this group (patient 3) had a heterozygous T1253M variant detected in the ABCA4 gene, in addition to the homozygous G1961E mutation. Login to comment

PMID: 22076985 [PubMed] Lazow MA et al: "Transition zones between healthy and diseased retina in choroideremia (CHM) and Stargardt disease (STGD) as compared to retinitis pigmentosa (RP)."

No. Sentence Comment

59 Characteristics of Patients with STGD Patient ID Eye Age Sex BCVA Mutation(s) (ABCA4) P8 12 OS 33 F 20/150 G1961E P9 2 OS 30 M 20/150 T1253M, G1961E P10 9817 OS 21 F 20/63 * P11 9 OS 19 M 20/150 IVS20ϩ5 GϾA, G1961E P12 6953 OD 49 F 20/50 * P13 11 OS 59 M 20/100 P1380L, S1696N P14 9831 OD 28 M 20/500 * P15 8813 OD 13 M 20/50 * P16 8 OS 34 M 20/100 G1961E, G1961E P17 6.1 OD 24 F 20/200 L541P/A1038V, G1961E P18 8833 OS 13 F 20/160 N965S, L2229P P19 8938 OD 13 M 20/200 A192T, R1300Q P20 5470 OD 28 F 20/100 * P21 9901 OS 41 M 20/160 I32V P22 9327 OS 11 F 20/63 G863A, A1695D P23 9386 OS 18 M 20/40 * P24 8862 OD 30 F 20/63 * P25 6.1 OD 21 F 20/150 L541P/A1038V, G1961E P26 6.2 OS 18 F 20/70 L541P/A1038V, G1961E P27 10 OS 23 F 20/150 L541P/A1038V, I1846T * Patient did not undergo genetic testing. Login to comment
31 Characteristics of Patients with STGD Patient ID Eye Age Sex BCVA Mutation(s) (ABCA4) P8 12 OS 33 F 20/150 G1961E P9 2 OS 30 M 20/150 T1253M, G1961E P10 9817 OS 21 F 20/63 * P11 9 OS 19 M 20/150 IVS20af9;5 Gb0e;A, G1961E P12 6953 OD 49 F 20/50 * P13 11 OS 59 M 20/100 P1380L, S1696N P14 9831 OD 28 M 20/500 * P15 8813 OD 13 M 20/50 * P16 8 OS 34 M 20/100 G1961E, G1961E P17 6.1 OD 24 F 20/200 L541P/A1038V, G1961E P18 8833 OS 13 F 20/160 N965S, L2229P P19 8938 OD 13 M 20/200 A192T, R1300Q P20 5470 OD 28 F 20/100 * P21 9901 OS 41 M 20/160 I32V P22 9327 OS 11 F 20/63 G863A, A1695D P23 9386 OS 18 M 20/40 * P24 8862 OD 30 F 20/63 * P25 6.1 OD 21 F 20/150 L541P/A1038V, G1961E P26 6.2 OS 18 F 20/70 L541P/A1038V, G1961E P27 10 OS 23 F 20/150 L541P/A1038V, I1846T * Patient did not undergo genetic testing. Login to comment

PMID: 21873672 [PubMed] Burke TR et al: "Quantification of peripapillary sparing and macular involvement in Stargardt disease (STGD1)."

No. Sentence Comment

112 Summary of Clinical, Demographic, and Genetic Data Patient Sex Age at Exam (y) Eye VA BCEA 1 SD (deg 2 ) Eccentricity of PRL (deg) ERG Group FAF Abnormalities Allele 1 Allele 2 Allele 3 Distribution Peripapillary Area 1 F 43 OS 20/20 0.73 0 II M - A1799D ND ND 2 M 30 OS 20/150 3.21 6 I M - T1253M G1961E ND 3 F 55 OD 20/30 1.82 0 I EM - G863A IVS28af9;5 Gb0e;T ND 4 M 44 OD 20/25 0.65 0 I M - E161K ND ND 5.1 F 24 OD 20/200 1.57 1 I M - L541P/A1038V G1961E ND 5.2 F 22 OD 20/30 2.74 1 I M - L541P/A1038V G1961E ND 6.1 F 21 OD 20/150 2.01 1 I M - L541P/A1038V G1961E ND 6.2 F 18 OS 20/100 3.09 4 I M - L541P/A1038V G1961E ND 7 F 27 OS 20/400 2.97 9* II EM Peripapillary atrophy L2027F G851D ND 8 M 34 OS 20/100 2.16 4 I M - G1961E G1961E ND 9 M 20 OS 20/150 2.77 4 I M - IVS20af9;5 Gb0e;A G1961E ND 10 F 23 OS 20/150 9.05 5 I M - L541P/A1038V I1846T ND 11 M 59 OS 20/100 6.52 10 II EM - P1380L S1696N ND 12 M 49 OD 20/150 9.97 1 I EM Nasalaf9;temporal flecks R1108H P1380L ND 13 M 47 OS 20/80 5.62 7 I EM - G863A Y106X ND 14 F 42 OD 20/200 9.53 9 I EM Temporal flecks N965S ND ND 15 M 14 OD 20/200 23.84 1 II EM Nasal flecks IVS38-10 Tb0e;C IVS40af9;5 Gb0e;A ND 16 M 52 OS 20/20 1.3 0 I M - IVS38-10 Tb0e;C ND ND 17 M 34 OS 20/30 2.8 1 I M - L541P/A1038V G1961E ND 18 F 33 OD 20/100 6 6 I M - G1961E R2077W ND 19 F 22 OS 20/60 11 4 I M - A854T A1038V C2150Y 20 F 34 OS 20/200 14.2 14 I EM - G1961E ND ND 21 F 19 OD 20/200 3.7 12 I EM - R602W M18821 ND 22 F 27 OD 20/400 9.6 9 II EM Peripapillary atrophy P1380L P1380L ND 23 F 18 OS 20/50 4.9 5 I EM - R1640W V1693I ND 24 M 22 OS 20/150 10.5 2 I EM - C54Y ND ND 25 M 44 OS 20/150 9.1 5 I EM - R1640W ND ND VA, visual acuity; Rel. Login to comment

PMID: 19217903 [PubMed] Cella W et al: "G1961E mutant allele in the Stargardt disease gene ABCA4 causes bull's eye maculopathy."

No. Sentence Comment

89 Of the compound heterozygous group, 5 patients from 2 families had the complex mutation L541P/A1038V, 2 patients (siblings) had the splicing mutation IVS20 þ 5G / A, and 5 patients had missense mutations Q636H, R2077W, T1253M, C54Y and D1532N (Table 1). Login to comment
131 In 5 patients (patients 7-11), missense mutations Q636H, R2077W, T1253M, C54Y and D1532N were found in addition to the G1961E allele, respectively. Login to comment
142 Case #, sex Age of onset Duration (years) Visual acuity (OD, OS) Allele 2 Bull`s eye type (FAF) SD-OCT MP-1 1, f 20 1 20/25, 20/40 G1961E (homozygous) B Not tested Not tested 2, f 49 13 20/200, 20/150 G1961E (homozygous) B Photoreceptor loss, thinner ONL and RPE atrophy Absolute scotoma in the central 4 degrees OD and in the central 6 degrees OS, eccentric PRL (superior retina) 3, m 19 13 20/70, 20/70 G1961E (homozygous) A Not tested Absolute scotoma in the central 6 degrees in both eyes, eccentric PRL (superior retina) 4.1, f 17 30 20/200, 20/200 L541P/A1038V B Not tested Not tested 4.2, m 28 2 20/25, 20/30 L541P/A1038V B Not tested Decreased sensitivity by 6 dB in the central 2 degrees in both eyes, foveal fixation 4.3, m 28 2 20/30, 20/40 L541P/A1038V B Not tested Decreased sensitivity by 9 dB OD and 11 dB OS in the central 2 degrees, foveal fixation 5.1, f 14 5 20/200, 20/400 L541P/A1038V C Photoreceptor loss (foveal optical gap), thinner ONL and normal RPE Decreased sensitivity by 8 dB in the central 2 degrees in both eyes, eccentric PRL (superior retina) 5.2, f 14 1 20/20, 20/25 L541P/A1038V A Photoreceptor disorganization, normal ONL and normal RPE Decreased sensitivity by 6 dB in the central 2 degrees in both eyes, foveal fixation 6.1, f 17 5 20/100, 20/100 IVS20 þ 5G / A C Photoreceptor loss, thinner ONL and RPE atrophy Absolute scotoma in the central 2 degrees in both eyes, eccentric PRL (superior retina) 6.2, m 14 3 20/40, 20/25 IVS20 þ 5G / A A Photoreceptor loss (foveal optical gap), thinner ONL and normal RPE Absolute scotoma in the central 2 degrees OD and decreased sensitivity by 18 dB in the central 2 degrees OS, eccentric PRL (superior retina) 7, m 28 12 20/200, 20/150 Q636H B Photoreceptor loss, thinner ONL and RPE atrophy Not tested 8, f 25 9 20/80, 20/25 R2077W B Not tested Not tested 9, m 67 2 20/800, 20/60 T1253M B Not tested Not tested 10, f 26 10 20/80, 20/80 C54Y B Not tested Not tested 11, f 44 20 20/400, 20/60 D1532N C Not tested Absolute scotoma in the central 8-10 degrees OD and absolute scotoma in the central 8 degrees OS, eccentric PRL (superior retina) Abbreviations: m, male; f, female; OD, right eye; OS, left eye; FAF, fundus autofluorescence; bull`s eye type A, presence of a ring of increase autofluorescence surrounding decreased autofluorescence; bull`s eye type B, decreased fovea autofluorescence without a surrounding ring of increase autofluorescence; bull`s eye type C, speckled macular appearance with slightly increased surround autofluorescence; SD-OCT, spectral-domain optical coherence tomography; ONL, outer nuclear layer; MP-1, microperimetry; and PRL, preferred retinal location. Login to comment
182 An exception was patient 9 with the missense mutation T1253M that imparts an amino acid change outside of ABCA4 functional domain and presented with poor visual acuity but uncertain disease duration. Login to comment
184 Finally, patient 8 had the missense mutation R2077W in addition to the G1961E allele and a mild-to-moderate phenotype, with asymmetrical visual acuity and discrete autofluorescence changes. Login to comment
143 Case #, sex Age of onset Duration (years) Visual acuity (OD, OS) Allele 2 Bull`s eye type (FAF) SD-OCT MP-1 1, f 20 1 20/25, 20/40 G1961E (homozygous) B Not tested Not tested 2, f 49 13 20/200, 20/150 G1961E (homozygous) B Photoreceptor loss, thinner ONL and RPE atrophy Absolute scotoma in the central 4 degrees OD and in the central 6 degrees OS, eccentric PRL (superior retina) 3, m 19 13 20/70, 20/70 G1961E (homozygous) A Not tested Absolute scotoma in the central 6 degrees in both eyes, eccentric PRL (superior retina) 4.1, f 17 30 20/200, 20/200 L541P/A1038V B Not tested Not tested 4.2, m 28 2 20/25, 20/30 L541P/A1038V B Not tested Decreased sensitivity by 6 dB in the central 2 degrees in both eyes, foveal fixation 4.3, m 28 2 20/30, 20/40 L541P/A1038V B Not tested Decreased sensitivity by 9 dB OD and 11 dB OS in the central 2 degrees, foveal fixation 5.1, f 14 5 20/200, 20/400 L541P/A1038V C Photoreceptor loss (foveal optical gap), thinner ONL and normal RPE Decreased sensitivity by 8 dB in the central 2 degrees in both eyes, eccentric PRL (superior retina) 5.2, f 14 1 20/20, 20/25 L541P/A1038V A Photoreceptor disorganization, normal ONL and normal RPE Decreased sensitivity by 6 dB in the central 2 degrees in both eyes, foveal fixation 6.1, f 17 5 20/100, 20/100 IVS20 &#fe; 5G / A C Photoreceptor loss, thinner ONL and RPE atrophy Absolute scotoma in the central 2 degrees in both eyes, eccentric PRL (superior retina) 6.2, m 14 3 20/40, 20/25 IVS20 &#fe; 5G / A A Photoreceptor loss (foveal optical gap), thinner ONL and normal RPE Absolute scotoma in the central 2 degrees OD and decreased sensitivity by 18 dB in the central 2 degrees OS, eccentric PRL (superior retina) 7, m 28 12 20/200, 20/150 Q636H B Photoreceptor loss, thinner ONL and RPE atrophy Not tested 8, f 25 9 20/80, 20/25 R2077W B Not tested Not tested 9, m 67 2 20/800, 20/60 T1253M B Not tested Not tested 10, f 26 10 20/80, 20/80 C54Y B Not tested Not tested 11, f 44 20 20/400, 20/60 D1532N C Not tested Absolute scotoma in the central 8-10 degrees OD and absolute scotoma in the central 8 degrees OS, eccentric PRL (superior retina) Abbreviations: m, male; f, female; OD, right eye; OS, left eye; FAF, fundus autofluorescence; bull`s eye type A, presence of a ring of increase autofluorescence surrounding decreased autofluorescence; bull`s eye type B, decreased fovea autofluorescence without a surrounding ring of increase autofluorescence; bull`s eye type C, speckled macular appearance with slightly increased surround autofluorescence; SD-OCT, spectral-domain optical coherence tomography; ONL, outer nuclear layer; MP-1, microperimetry; and PRL, preferred retinal location. Login to comment

PMID: 11726554 [PubMed] Shroyer NF et al: "Cosegregation and functional analysis of mutant ABCR (ABCA4) alleles in families that manifest both Stargardt disease and age-related macular degeneration."

No. Sentence Comment

43 Of note, AR468-8 was heterozygous for three mutations: the transitions 3758C→T (encoding the missense mutation T1253M), 4139C→T (encoding the missense mutation P1380L) and 5882G→A (encoding the missense mutation G1961E). Login to comment
44 Segregation analysis in this family revealed that two alterations (T1253M and G1961E) were on the same chromosome; thus AR468-8 is compound heterozygous for a novel complex allele [T1253M; G1961E] and the missense mutation P1380L (Fig. 1). Login to comment
47 Two novel mutations were identified in this cohort: the missense mutation T1253M was identified as part of the complex allele [T1253M; G1961E] and the transition 1648G→A (encoding the missense mutation G550R) was identified in STGD-affected AR484-4. Login to comment

PMID: 26593885 [PubMed] Sciezynska A et al: "Next-generation sequencing of ABCA4: High frequency of complex alleles and novel mutations in patients with retinal dystrophies from Central Europe."

No. Sentence Comment

99 The third ABCA4 complex allele contained the previously reported p.T1253M present in cis with p.G1961E (Paloma et al., 2001). Login to comment
101 [(T1253M; G1961E)] complex allele, the p.G1961E mutation was identified in 21 other unrelated probands, which makes it the second most frequent disease-causing ABCA4 change in our patients. Login to comment
151 [(T1253M; G1961E)] (1/184) x x ZGM: exome data for the Polish population; The number of mutant and total alleles detected is given in brackets; x e no ABCA4 diseases-associated variant detected. Login to comment