ABCA4 p.Trp855*
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PMID: 22247458
[PubMed]
Cideciyan AV et al: "Macular function in macular degenerations: repeatability of microperimetry as a potential outcome measure for ABCA4-associated retinopathy trials."
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42
Clinical and Molecular Characteristics of the ABCA4 Patients Patient Age (y)/Sex ABCA4 Mutation Clinical Diagnosis Visual Acuity* Kinetic Visual Field Extent (V-4e)†Allele 1 Allele 2 Foveal Fixation P1‡ 12/M N965S W821R STGD 20/20 97 P2‡ 17/F V989A IVS28ϩ5 GϾT STGD 20/100 90 P3 18/M G1961E R1129L§ STGD 20/100 105 P4 21/F R212C P68R STGD 20/125 101 P5 24/M P1511 del1ccgC R1705Q STGD 20/25 114 P6 31/M G863A R1108C STGD 20/25 105 P7 32/F IVS40ϩ5 GϾA V935A STGD 20/32 103 P8 34/M G1961E - CRD 20/32 98 P9 37/F R681X P309R STGD 20/20 109 P10 39/M G1961E C54Y§ STGD 20/40 101 P11‡ 42/F G1961E V256V STGD 20/32 105 P12‡ 46/F G1961E V256V STGD 20/32 106 P13 52/F G1961E P1380L STGD 20/40 105 P14 58/M D600E R18W§ STGD 20/40 84 Extrafoveal Fixation P15 11/M V256V T1526M CRD 20/200 102 P16 15/M C54Y IVS35ϩ2 TϾC STGD 20/200 96 P17‡ 16/F V989A IVS28ϩ5 GϾT STGD 20/100 100 P18‡ 16/M N965S W821R STGD 20/125 100 P19 19/F A1038V/L541P N965S STGD 20/400 90 P20 21/M G863A IVS35ϩ2 TϾC STGD 20/200 99 P21 22/F G1961E R152X STGD 20/50 104 P22 27/M G863A P1660S§ STGD 20/100 98 P23 27/F G1961E A1038V/L541P STGD 20/100 109 P24 29/M G1961E T1019M STGD 20/100 104 P25 33/M P1486L deletion of exon 7 STGD 20/400 98 P26 36/F G863A C1490Y STGD 20/100 93 P27 41/M A1038V/L541P - STGD 20/125 108 P28 49/F T1526M R2030Q STGD 20/125 98 P29 55/F W855X - STGD 20/160 87 P30 56/F G1961E IVS37ϩ1 GϾA§ STGD 20/125 89 P31 60/F G1961E M669 del2ccAT STGD 20/125 104 STGD, Stargardt disease; CRD, cone-rod dystrophy.
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ABCA4 p.Trp855* 22247458:42:1441
status: NEWX
ABCA4 p.Trp855* 22247458:42:1451
status: NEW
PMID: 19365039
[PubMed]
Roberts LJ et al: "Clinical utility of the ABCR400 microarray: basing a genetic service on a commercial gene chip."
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36
Case RPS1111.1, a Black African Xhosa-speaking individual with STGD, was found not to carry the homozygous c.2565GϾA (W855X) mutation that was detected using the chip.
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ABCA4 p.Trp855* 19365039:36:124
status: NEW50 A, Electropherogram showing the exon 16 sequence spanning the homozygous 2565delGTACCTTG identified instead of the W855X mutation in individual RPS1111.1.
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ABCA4 p.Trp855* 19365039:50:115
status: NEW100 The novel 2565delGTACCTTG variation was also incorrectly identified by the ABCR400 microarray as the W855X mutation (Figure 1).
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ABCA4 p.Trp855* 19365039:100:101
status: NEW101 The presence of this deletion causes the sequence at position 855 to be that expected from the W855X mutation (TGGϾTGA).
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ABCA4 p.Trp855* 19365039:101:95
status: NEW38 Case RPS1111.1, a Black African Xhosa-speaking individual with STGD, was found not to carry the homozygous c.2565Gb0e;A (W855X) mutation that was detected using the chip.
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ABCA4 p.Trp855* 19365039:38:124
status: NEW52 A, Electropherogram showing the exon 16 sequence spanning the homozygous 2565delGTACCTTG identified instead of the W855X mutation in individual RPS1111.1.
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ABCA4 p.Trp855* 19365039:52:115
status: NEW102 The novel 2565delGTACCTTG variation was also incorrectly identified by the ABCR400 microarray as the W855X mutation (Figure 1).
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ABCA4 p.Trp855* 19365039:102:101
status: NEW103 The presence of this deletion causes the sequence at position 855 to be that expected from the W855X mutation (TGGb0e;TGA).
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ABCA4 p.Trp855* 19365039:103:95
status: NEW
PMID: 12192456
[PubMed]
Gerth C et al: "Phenotypes of 16 Stargardt macular dystrophy/fundus flavimaculatus patients with known ABCA4 mutations and evaluation of genotype-phenotype correlation."
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81
Patient 2 had a Table 2 Identified mutations in the ABCR alleles in the 16 patients (ND not tested) Patient ABCA4 allele 1 ABCA4 allele 2 no./sex (1*) Nucleotide changes Effects Nucleotide changes Effects 1a/F (139) 5917delG Frameshift 5917delG Frameshift 1b/F(139b) 5917delG Frameshift 5882G→A G1961E 2/M (167) IVS 40+5G→A Splice 4463G→A C1488Y 3/F (108) IVS 40+5G→A Splice 1086T→A Y362X 4/M (109) 1622T→C- L541P-A1038V 2564G→A W855X 3113C→T 5/F (113) 1622T→C- L541P-A1038V 2588G→C Splice 3113C→T 6/M (50) 2588G→C Splice 3113C→T A1038V 7b/M (138) 2588G→C Splice IVS13+1G→A Splice 7a/F Not tested Splice Not tested Splice 8/F (111) 5882G→A G1961E 2292delT-2295T→G Frameshift-S765R 9/F (147) 5882G→A G1961E IVS36+1G→A Splice 10/F (41) 5882G→A G1961E 2041C→T R681X 11a/F (114) 5882G→A G1961E 6609C→A Y2203X 11b/M ND ND 12/F (148) 3292C→T R1097C 6609C→A Y2203X 13/M (107) 3528insTGCA Frameshift 2291G→A C764Y* Refers to the patients` ID in [42] Table3Demographicdataandclinicalfeaturesofthe16patients(NDtestnotdone,Aabnormal,Nnormal,RreducedArdenratio,NRnotreliable,NAmfERGnotanalyz- able,+present,-absent,DCdarkchoroid,DDdiscdiameter) Pat.aAgeDiseaseVisualacuityColorFun-GanzfeldERGEOGmfERGStatictwo-colorKineticperimetryAngio-FundusAF atdurationvisiondusbthresholdperimetrygraphy onset/(years)ODOSRodMaximalConePeakResponseCentralCon-CentralCircularPeri- examresponseresponseresponsetimesdensitiesMeanRSLMeanCSLscotomacentricAFAFmacular/ b-wavecb-wavec30Hzab-abnormalc(dB)e(dB)efortargetcon-AF flickerdnormaldstriction <=13°>13°<=13°>13° 1a5/10520/250*20/250NDIfNDNANAND-ND-NRNRND+-- 1b32/32020/30*20/30NDINDNNNDN5-10°ND-ND-NDNDND+-- 27/15820/10020/200*AIINNNND5-15°5-25°2120--ND+-+ 39/13420/250*20/250AIINNNN5-15°5-25°0030I-2e-ND+++ 47/12520/25020/250*AIIINNNN5-25°5-25°ND-ND-I-4e-ND>1DD-- 520/4525<20/400<20/400*AIIINNNNNANA194143II-3e+ND>1DD-+ 614/19520/200*20/200AIINDNNNR5-10°5-25°1080I-4e-ND+-+ 7b16/23720/25020/250*AIINDNNR20°5-25°101113I-3e-ND+-+ 7a6/272120/20020/200NDIINDNDNDNDND-ND-ND-NDNDNDND 815/18320/100*20/100AINNND5-10°5-25°2010I-2e-N++- 921/23220/40*20/200AINDNNN10-15°5°0060NDNDN+++ 1024/31720/400*20/400AIINNNN5°5-15°3270I-2e-ND+-+ 11a16/331720/200*20/200AIINDNNNN5-15°81140I-2e-NDND 11b26/28220/20020/200*AINNNN5-10°,5-10°0010I-2e-ND+++ 20-25° 1238/571920/22*20/250NDIII(OD)ND5-25°5-25°35/3835/39ND-III/4e-NDND 1314/16220/100*20/100AIINDNNNN5-25°1120ND-DC+-+ aOnenumberindicatesonefamily bReferredtoTable1 cResults<5thpercentile dResults>95thpercentile eRSL(rodsensitivityloss;500nm,darkadapted)andCSL(conesensitivityloss; 600nm,lightadapted)comparedtothe10thpercentileofnormals;mfERGrespons- eswereanalyzedforallbutthecentral(1°inradius)responseduetohighnoise fRetinalvesselattenuation *EyetestedformfERG/staticperimetry CSL within 13° and a more widespread RSL over the 30° test field.
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ABCA4 p.Trp855* 12192456:81:471
status: NEWX
ABCA4 p.Trp855* 12192456:81:478
status: NEW84 Patients with the complex mutation L541P-A1038V Two patients were compound heterozygous for this complex mutation and a nonsense mutation (W855X, patient 4) as well as a mutation with bipartite outcome [2588G→C (G863A/G863del), patient 5].
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ABCA4 p.Trp855* 12192456:84:139
status: NEW158 The slightly more advanced cone dysfunction in patient 3 could be caused by the more severe functional restrictions of the associated nonsense mutation (Y362X), which results in a non-functional gene product.
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ABCA4 p.Trp855* 12192456:158:131
status: NEW159 The complex mutation L541P-A1038V was associated with an earlier onset and more rapid progression when occurring together with the W855X nonsense mutation (patient 4) than with the missense mutation 2588G→C (patient 5).
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ABCA4 p.Trp855* 12192456:159:131
status: NEW160 Both mutations on their own, L541P and A1038V, have been associated with severely reduced but not abolished ATPase activity [49].
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ABCA4 p.Trp855* 12192456:160:21
status: NEW161 The combination with W855X, which completely eliminates the ATPase activity, predicts a severe phenotype, which is supported by the functional data of patient 4.
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ABCA4 p.Trp855* 12192456:161:21
status: NEW
PMID: 10958763
[PubMed]
Rivera A et al: "A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration."
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Nucleotide alterations occurring in sim- Table 2 ABCA4 Mutations Found in Patients with STGD and AMD and in Controls EXON AND NUCLEOTIDE CHANGE EFFECT NO. OF ALLELES REFERENCE(S) STGD (288) AMD (400) Control (440) 3: 178GrA A60T 1 0 0 This study 179CrT A60E 1 0 0 This study 194GrA G65E 1 0 0 Fishman et al. (1999) 203CrT P68L 1 0 0 This study 214GrA G72R 1 0 0 This study 296insA Frameshift 2 0 0 This study 5: 454CrT R152X 1 0 0 This study 6: 634CrT R212C 1 0 0 Lewis et al. (1999) 688TrA C230S 1 0 0 This study 730delCT Frameshift 1 0 0 This study 740ArG N247S 1 0 0 This study 768GrT Splice 2 0 0 Maugeri et al. (1999) 8: 983ArT E328V 1a 0 0 This study 1086TrA Y362X 1 0 0 This study 10: 1317GrA W438X 1 0 0 This study 11: 1411GrA E471K 1 0 0 Lewis et al. (1999) 12: 1622TrC L541P 21a 1a 0 Rozet et al. (1998), Fishman et al. (1999), Lewis et al. (1999), Maugeri et al. (1999) 1715GrA R572Q 1a 0 0 Lewis et al. (1999) 13: 1819GrA G607R 1 0 0 This study 1903CrA Q635K 2a 0 0 This study 1903CrT Q635X 1 0 0 This study IVS13ϩ1GrA Splice 2 0 0 This study 14: 1957CrT R653C 1 0 0 This study 1988GrA W663X 1 0 0 This study 2041CrT R681X 4 0 0 Maugeri et al. (1999) 15: 2291GrA C764Y 1 0 0 This study 2292delT Frameshift 1a 0 0 This study 2295TrG S765R 1a 0 0 This study 16: 2564GrA W855X 1 0 0 Nasonkin et al. (1998) 17: 2588GrC Spliceb 17a 6 5 Allikmets et al. (1997a), Cremers et al. (1998), Lewis et al. (1999), Maugeri et al. (1999), Papaioannou et al. (2000) 18: 2701ArG T901A 0 2 0 This study 2741ArG H914A 0 0 1 This study 19: 2876CrT T959I 1 0 0 This study 20: IVS20ϩ5GrA Splice 1 0 0 This study 21: 3106GrA E1036K 1a 0 0 Nasonkin et al. (1998) 3113CrT A1038V 26a 4a 1 Allikmets et al. (1997a), Cremers et al. (1998), Rozet et al. (1998), Fishman et al. (1999), Lewis et al. (1999), Maugeri et al. (1999) T3187TrC S1063P 1 0 0 This study (Continued) 805 Table 2 Continued EXON AND NUCLEOTIDE CHANGE EFFECT NO. OF ALLELES REFERENCE(S) STGD (288) AMD (400) Control (440) 22: 3292CrT R1097C 1 0 0 This study 3322CrT R1108C 4 0 0 Rozet et al. (1998), Fishman et al. (1999), Lewis et al. (1999) 24: 3528insTGCA Frameshift 1 0 0 This study 25: 3808GrT E1270X 1 0 0 This study 27: 3898CrT R1300X 1 0 0 This study 28: IVS28ϩ5GrA Splice 1 0 0 This study 4139CrT P1380L 1 0 0 Lewis et al. (1999) 4195GrA E1399K 2 0 0 This study 4234CrT Q1412X 4 0 0 Maugeri et al. (1999) 29: 4289TrC L1430P 2 0 0 This study 4318TrG F1440V 1 0 0 This study 4328GrA R1443H 1 0 0 This study 30: 4457CrT P1486L 1 0 0 Lewis et al. (1999) 4463GrA C1488Y 1 0 0 This study 31: 4610CrT T1537M 1 0 0 This study 35: IVS35ϩ2TrA Splice 1 0 0 This study 36: 5065TrC S1689P 1 0 0 This study 5114GrT R1705L 1 0 0 This study IVS36ϩ1GrA Splice 1 0 0 This study 37: 5198TrC M1733T 0 0 1 This study 5242GrA G1748R 1 0 0 This study 5248CrT Q1750X 1 0 0 This study 5288TrC L1763P 1 0 0 This study 38: IVS38ϩ1GrA Splice 1 0 0 This study 40: 5653GrA E1885K 1 0 0 This study 5693GrA R1898H 5 2 1 Allikmets et al. (1997b), Lewis et al. (1999) IVS40ϩ5GrA Splice 8a 0 0 Cremers et al. (1998), Lewis et al. (1999), Maugeri et al. (1999) 42: 5882GrA G1961E 34 4 2 Allikmets et al. (1997b), Fishman et al. (1999), Lewis et al. (1999), Maugeri et al. (1999) 43: 5917delG Frameshift 3 0 0 This study 5923GrC G1975R 1 0 0 This study 5929GrA G1977S 1 0 0 Rozet et al. (1998), Lewis et al. (1999) 45: 6229CrG R2077G 1 0 0 This study 6229CrT R2077W 1 0 0 Allikmets et al. (1997a), Fishman et al. (1999), Lewis et al. (1999) 48: 6609CrA Y2203X 2 0 0 This study 6647GrT A2216V 0 0 1 This study a Mutation pairs occurring on a single haplotype.
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ABCA4 p.Trp855* 10958763:80:1288
status: NEW111 Likewise, for the intron 28 alteration, a spliced product Table 5 Patients with STGD Who Have Two Identified Disease Alleles AGE AT ONSET AND PATIENT MUTATION SEGREGATION IN FAMILY a Allele 1 Allele 2 5-9 years: STGD17 Q1412X R2077W Yes STGD88 G65E G1961E NA STGD93 G1961E G1961E Yes STGD99 L541P-A1038V G1961E Yes STGD100 L541P-A1038V IVS40ϩ5GrA Yes STGD108 Y362X IVS40ϩ5GrA Yes STGD109 L541P-A1038V W855X Yes STGD139b 5917delG 5917delG Yes STGD167 C1488Y IVS40ϩ5GrA Yes 10-14 years: STGD21 R681X R1898H NA STGD37 L541P-A1038V L541P-A1038V Yes STGD47/164 IVS13ϩ1GrA 2588GrC Yes STGD50 2588GrC A1038V NA STGD70 2588GrC IVS40ϩ5GrA NA STGD82 L541P-A1038V S1063P Yes STGD87 2588GrC Q1750X Yes STGD98 R212C T959I Yes STGD102 R572Q-2588GrC IVS35ϩ2TrA Yes STGD107 C764Y 3528ins4 Yes STGD120 L1430P L1430P NA STGD121 R1300X IVS40ϩ5GrA Yes STGD156 R1108C G1961E NA STGD159 R1108C Q1412X Yes STGD171 L541P-A1038V G1961E NA 15-19 years: STGD34 G768T G1961E Yes STGD39 L541P-A1038V R1443H NA STGD40/163 2588GrC E1885K Yes STGD45 E1399K G1977S Yes STGD59 R1898H G1975R NA STGD67 P68L S1689P Yes STGD75 Q635K IVS40ϩ5GrA Yes STGD111 2292delT-S765R G1961E Yes STGD114 Y2203X G1961E Yes STGD138 IVS13ϩ1GA 2588GrC Yes 20-24 years: STGD41 R681X G1961E Yes STGD63 A60T R1898H NA STGD86 296insA G1961E Yes STGD91 L541P-A1038V A1038V NA STGD113 L541P-A1038V 2588GrC Yes STGD118b IVS20ϩ5GrA G1961E Yes STGD119 L541P-A1038V G1961E Yes STGD122 L541P-A1038V G1961E Yes STGD135 W663X G1961E NA STGD147 IVS36ϩ1GrA G1961E Yes STGD168 L541P-A1038V G1961E NA 25-29 years: STGD62 G607R G1961E NA STGD71 296insA A1038V Yes STGD78 2588GrC Q1412X Yes STGD103 2588GrC IVS20ϩ5GrA Yes STGD116 L541P-A1038V G1961E Yes STGD139bb G1961E 5917delG Yes у30 years: STGD38 E471K G1961E Yes STGD68 E1399K G1961E Yes STGD69 L541P-A1038V 2588GrC NA STGD95 F1440V G1748R Yes STGD134 C230S G1961E NA STGD144 2588GrC R1705L NA STGD148 R1097C Y2203X NA STGD170 L541P-A1038V 2588GrC NA a NA p not applicable.
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ABCA4 p.Trp855* 10958763:111:416
status: NEW