ABCMdb

PMID: 20335603

Poloschek CM, Bach M, Lagreze WA, Glaus E, Lemke JR, Berger W, Neidhardt J
ABCA4 and ROM1: implications for modification of the PRPH2-associated macular dystrophy phenotype.
Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4253-65. Epub 2010 Mar 24., [PubMed]

Sentences

No. Mutations Sentence Comment

9 ABCA4 p.Val2050Leu Patients with heterozygous sequence alterations only in ROM1 (p.R229H) or ABCA4 (p.V2050L) showed a mild ocular phenotype and were otherwise asymptomatic. Login to comment 70 ABCA4 p.Val2050Leu ABCA4 p.Val2050Leu It is predicted to lead to an amino acid substitution (valine to leucine at position 2050, p.V2050L). Login to comment 73 ABCA4 p.Val2050Leu ABCA4 p.Val2050Leu It is predicted to lead to an amino acid substitution (valine to leucine at position 2050, p.V2050L). Login to comment 100 ABCA4 p.Val2050Leu Group 3: Mutations in PRPH2, ROM1, and ABCA4 (p.R172W, p.R229H, and p.V2050L). Login to comment 103 ABCA4 p.Val2050Leu Group 3: Mutations in PRPH2, ROM1, and ABCA4 (p.R172W, p.R229H, and p.V2050L). Login to comment 121 ABCA4 p.Val2050Leu Group 5: Mutation of ABCA4 (p.V2050L). Login to comment 124 ABCA4 p.Val2050Leu Group 5: Mutation of ABCA4 (p.V2050L). Login to comment 140 ABCA4 p.Val2050Leu ABCA4 p.Val2050Leu Detailed Phenotypic Data of All Examined Family Members Sorted by Groups Patient Group Genotype Age At Ex. VA OD/OS Age (y) at Onset of Symptoms Visual Field Color Vision (Panel D 15) Fundus FAF ERG Scotopic 1.8 B-Wave Amplitude ERG 30-Hz Flicker Amplitude mfERG EOG Arden Ratio III-2 2 p.R172W, p.R229H 84 0.05/0.02 56; photophobia 30; VA loss GP stable OU: not possible OU: severe MA OU: NR due to dense cataracts P 2 P 2 Z 4 P 2 71 0.02/0.03 GP: OU sup VF loss, OS inf, VF constriction to 70&#b0; OU: not possible OU: severe MA ND ND ND ND ND V-4 3 p.R172W, p.V2050L, p.R229H 22 1.0/1.2 22; photophobia in bright light 22; mild nyctalopia GP: OU sup mild constriction (I/3, I/2, I/1), OS paracentral scotoma 5&#b0; (I/1), OP: reduction central 20&#b0; OU: normal OU: mild-moderate MA OU: speckled, 3 ODD, encircling increase P 1 N Z 3 N IV-4 3 p.R172W, p.V2050L, p.R229H 50 0.2/0.3 49; nyctalopia 40; photophobia 35; VF defects 13; mild VA loss GP: OD paracentral scotoma (III/4) 10&#b0;, sensitivity loss for I/1, I/2, OS central scotoma 40&#b0; (I/3) extending temporally OU: marked protan and deutan defects OU: moderate MA extending beyond arcades; temporally b0e;1 ODD severe MA; midperipheral RPE clumping; moderate temporal ON atrophy OU: speckled beyond arcades, reduced CTA (mild progression) P 3 P 2 Z 5 P 1 48 0.2/0.5 40; photophobia 35; VF defects 13; mild VA loss GP: OD central scotoma 35&#b0; (I/3) extending temporally, OS central scotoma 40&#b0; (I/3) OD: marked protan and deutan defects OS: marked protan, deutan, and tritan defects OU: mild pericentral MA to arcades; mid-peripheral RPE clumping; nasally 1 ODD RPE atrophy; moderate temporal ON atrophy OU: speckled beyond arcades, reduced CTA P 2 P 2 Z 5 ND IV-9 4 p.R229H 36 1.25/1.25 Asymptomatic OP and GP: normal OS: unsaturated: 2 unspecific defects OU: normal OU: normal N N Z 1 N (continues) nantly affected with stable rod function. Login to comment 141 ABCA4 p.Val2050Leu ABCA4 p.Val2050Leu TABLE1.DetailedPhenotypicDataofAllExaminedFamilyMembersSortedbyGroups Patient Group Genotype Age AtEx. VA OD/OS Age(y)at Onsetof SymptomsVisualField ColorVision (PanelD15)FundusFAF ERG Scotopic 1.8B-Wave Amplitude ERG30-Hz Flicker AmplitudemfERG EOG Arden Ratio V-21 p.R172W 221.25/1.25AsymptomaticOP:ODnasalsup smallscotoma, OSnormal;GP: ODnormal ODdesaturated:2 unspecific defects OU:ONdrusen, perifoveolar drusenODϾOS OU:ONdrusen, peri-foveolar punctual increase ODϾOS P1NNODN OSdesaturated:1 unspecific defect OSNA IV-71 p.R172W 450.2/0.140;VAloss35; photophobia GP:OUcentral scotoma40° (I/2) OD:mildprotan, deutanand tritandefects, OS:unspecific defects OU:macularRPE granularity,OS: 0.5ODD temporalMA OU:speckled beyondarcades; OS:reducedat lowerarcade indicating atrophy,1ODD NNZ5ND* III-41 p.R172W 750.05/0.0742;VAloss photophobia (onset unknown) GP:OUcentral scotoma30° (I/3) OU:marked protanand deutandefects OU:severeMA, 4ODD OU:reduced CTA,4ODD, surrounding speckles NP2AP1 V-12 p.R172W, p.R229H 260.9/0.922;flickering lightsensation OP:ODnormal OSparacentral defects10° fromcenter OU:normalOU:mildmacular RPEclumping OU:speckled, 2ODD, surrounding increase,OD: reticular increase P1P1Z3N 21AsymptomaticNReNReNReNDNDNDZ1ND IV-12 p.R172W, p.R229H 560.8/0.7501adaptation difficulties GP:OUparacentral scotoma:1-10° radius(I/2,I/3 inf,I/4sup) OU:mild unspecific defectsOS:1 tritandefect OU:mildRPE atrophy OU:speckled, 3ODD NP1Z4P1 32;photophobiaOP:asinGPOD:moderate temporaloptic nerveatrophy 30;flickering lightsensation, relative paracentral scotoma 471.0/1.032;photophobiaGP:OUstableNDOU:mildRPE irregularity NDNDNDZ3ND 430.9/0.930;flickering lightsensation, relative paracentral scotoma GP:OU paracentral scotoma:3-10° radius(I/2inf, I/4sup) OU:moderate tetartandefects OU:minorRPE irregularity NDP2NNDP1 (continues) TABLE1(continued).DetailedPhenotypicDataofAllExaminedFamilyMembersSortedbyGroups Patient Group Genotype Age AtEx. VA OD/OS Age(y)at Onsetof SymptomsVisualField ColorVision (PanelD15)FundusFAF ERG Scotopic 1.8B-Wave Amplitude ERG30-Hz Flicker AmplitudemfERG EOG Arden Ratio III-22 p.R172W, p.R229H 840.05/0.0256;photophobia 30;VAloss GPstableOU:notpossibleOU:severeMAOU:NRdueto dense cataracts P2P2Z4P2 710.02/0.03GP:OUsupVF loss,OSinf,VF constriction to70° OU:notpossibleOU:severeMANDNDNDNDND V-43 p.R172W, p.V2050L, p.R229H 221.0/1.222;photophobia inbrightlight 22;mild nyctalopia GP:OUsupmild constriction (I/3,I/2,I/1), OSparacentral scotoma5° (I/1),OP: reduction central20° OU:normalOU:mild- moderateMA OU:speckled,3 ODD, encircling increase P1NZ3N IV-43 p.R172W, p.V2050L, p.R229H 500.2/0.349;nyctalopia 40;photophobia 35;VFdefects 13;mildVAloss GP:OD paracentral scotoma(III/4) 10°,sensitivity lossforI/1,I/2, OScentral scotoma40° (I/3)extending temporally OU:marked protanand deutandefects OU:moderateMA extendingbeyond arcades; temporallyϾ1 ODDsevereMA; midperipheral RPEclumping; moderate temporalON atrophy OU:speckled beyond arcades, reducedCTA (mild progression) P3P2Z5P1 480.2/0.540;photophobia 35;VFdefects 13;mildVAloss GP:ODcentral scotoma35° (I/3)extending temporally,OS centralscotoma 40°(I/3) OD:marked protanand deutandefects OS:marked protan,deutan, andtritan defects OU:mild pericentralMAto arcades;mid- peripheralRPE clumping;nasally 1ODDRPE atrophy; moderate temporalON atrophy OU:speckled beyond arcades, reducedCTA P2P2Z5ND IV-94 p.R229H 361.25/1.25AsymptomaticOPandGP: normal OS:unsaturated:2 unspecific defects OU:normalOU:normalNNZ1N (continues) nantly affected with stable rod function. Login to comment 154 ABCA4 p.Val2050Leu The ABCA4 p.V2050L heterozygous carrier reported herein (group 5, V-3) showed centrally reduced mfERG amplitudes and additional minor fundus abnormalities. Login to comment 155 ABCA4 p.Val2050Leu ABCA4 p.Val2050Leu The ABCA4 p.V2050L heterozygous carrier reported herein (group 5, V-3) showed centrally reduced mfERG amplitudes and additional minor fundus abnormalities. Login to comment 156 ABCA4 p.Val2050Leu ABCA4 p.Val2050Leu This finding suggests that the p.V2050L mutation in the heterozygous state is capable of mildly reducing macular function without an additional mutation on the second allele. Login to comment 157 ABCA4 p.Val2050Leu Indeed, heterozygous mutations in ABCA4 have been reported to cause electrophysiologically detectable dysfunction in individuals who had no obvious clinical signs: Maia-Lopes et al.40 described and clinically characterized a heterozygous ABCA4 p.V2050L carrier within a family with Stargardt disease. Login to comment 159 ABCA4 p.Val2050Leu In contrast, normal flicker amplitudes and stable rod function as shown in a follow-up examination 13 years after the initial presentation was found in her brother (group 2, IV-1) not carrying ABCA4 p.V2050L. Login to comment 160 ABCA4 p.Val2050Leu ABCA4 p.Val2050Leu In contrast, normal flicker amplitudes and stable rod function as shown in a follow-up examination 13 years after the initial presentation was found in her brother (group 2, IV-1) not carrying ABCA4 p.V2050L. Login to comment 161 ABCA4 p.Val2050Leu ABCA4 p.Val2050Leu ABCA4 p.Val2050Leu This finding may hint at an additional effect of p.V2050L on generalized cone function and an acceleration of loss of rod function if the genotype also contains ROM1 p.R229H and PRPH2 TABLE1(continued).DetailedPhenotypicDataofAllExaminedFamilyMembersSortedbyGroups Patient Group Genotype AgeAt Ex. VA OD/OS Age(y)at Onsetof SymptomsVisualField ColorVision (PanelD15)FundusFAF ERG Scotopic 1.8B-Wave Amplitude ERG30-Hz Flicker AmplitudemfERG EOG Arden Ratio III-64 p.R229H 681.0/1.0AsymptomaticOPandGP: normal OS:unsaturated:1 unspecific defect OU:mildarteriolar narrowing; arteriovenous nipping OU:normalNNZ2N V-35 p.V2050L 241.25/1.25AsymptomaticOPandGP: Normal ODdesaturated:1 unspecific defect OU:minimal perifoveolarRPE irregularity OU:subtle perifoveolar increase NNZ2N A,globalamplitudereduction;arcades,temporalvasculararcades;CTA,correspondingtoatrophy;EOG,electrooculogram;ERG,full-fieldelectroretinogram;ex.,examination;FAF,fundus autofluorescence;GP,Goldmannperimetry;inf,inferior;MA,macularatrophy;mfERG,multifocalelectroretinogram;NA,notanalyzableduetoartifact;N,normal;ND,notdone;ND*,notdonebecause patientrefusedtheexamination;NL,normallimit;NR,notrecordable;NR,norecords;ON,opticnerve;OP,Octopusperimetry;P1-3,amplitude(ERG)orArdenratio(EOG,normalrange1.7-3.3) belowthelowernormallimit(increasingreduction);ODD,opticdiscdiameter;sup,superior;VA,visualacuity;VF,visualfield;Z1-5,pleaseseeMethodsforanexplanation.Alldegreesindicate diameterunlessotherwiseindicated. Login to comment 163 ABCA4 p.Val2050Leu ABCA4 p.Val2050Leu In support of this idea, it has been reported previously that ABCA4 p.V2050L can be associated with a rod-cone pattern of functional loss as described in one patient with RP who bears a heterozygous p.V2050L mutation. Login to comment 164 ABCA4 p.Val2050Leu ABCA4 p.Val2050Leu In support of this idea, it has been reported previously that ABCA4 p.V2050L can be associated with a rod-cone pattern of functional loss as described in one patient with RP who bears a heterozygous p.V2050L mutation. Login to comment