ABCMdb

PMID: 9973280

Lewis RA, Shroyer NF, Singh N, Allikmets R, Hutchinson A, Li Y, Lupski JR, Leppert M, Dean M
Genotype/Phenotype analysis of a photoreceptor-specific ATP-binding cassette transporter gene, ABCR, in Stargardt disease.
Am J Hum Genet. 1999 Feb;64(2):422-34., [PubMed]

Sentences

No. Mutations Sentence Comment

2 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val The two most common mutant alleles, G1961E and A1038V, each identified in 16 of 173 disease chromosomes, composed 18.5% of mutations identified. Login to comment 3 ABCA4 p.Gly1961Glu G1961E has been associated previously, at a statistically significant level in the heterozygous state, with age-related macular degeneration (AMD). Login to comment 76 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala ABCA4 p.Arg212Cys ABCA4 p.Leu541Pro ABCA4 p.Leu1970Phe ABCA4 p.Gly1977Ser ABCA4 p.Cys1488Arg ABCA4 p.Cys54Tyr ABCA4 p.Cys1490Tyr ABCA4 p.Cys75Gly ABCA4 p.Arg2139Trp ABCA4 p.Arg2149* ABCA4 p.Arg602Trp ABCA4 p.Asn965Ser ABCA4 p.Val2050Leu ABCA4 p.Glu2131Lys ABCA4 p.Arg2106Cys ABCA4 p.Arg2038Trp ABCA4 p.Arg2030* ABCA4 p.Leu2027Phe ABCA4 p.Pro68Arg ABCA4 p.Thr1526Met ABCA4 p.Arg1108Cys ABCA4 p.Arg2030Gln ABCA4 p.Trp821Arg ABCA4 p.Pro1380Leu ABCA4 p.Pro1486Leu ABCA4 p.Arg1898His ABCA4 p.Leu1201Arg ABCA4 p.Glu1087Lys ABCA4 p.Val931Met ABCA4 p.Phe1440Ser ABCA4 p.Trp1408Arg ABCA4 p.Ser1696Asn ABCA4 p.Arg1129Leu ABCA4 p.Arg2077Trp ABCA4 p.Phe608Ile ABCA4 p.Glu471Lys ABCA4 p.Glu1122Lys ABCA4 p.Glu2096Lys ABCA4 p.Val1433Ile ABCA4 p.Asp1532Asn ABCA4 p.Gly818Glu ABCA4 p.Gly1886Glu ABCA4 p.Asp645Asn ABCA4 p.His1838Tyr ABCA4 p.Arg572Gln ABCA4 p.Tyr639* ABCA4 p.Ala60Val ABCA4 p.Trp697* ABCA4 p.Ser336Cys ABCA4 p.Asp846His ABCA4 p.His1406Tyr ABCA4 p.Arg24His ABCA4 p.Arg943Trp ABCA4 p.Arg1129Cys ABCA4 p.Asp249Gly ABCA4 p.Gly851Asp ABCA4 p.Val1072Ala ABCA4 p.Tyr340Asp ABCA4 p.Arg572Pro ABCA4 p.Trp1449* ABCA4 p.Arg1820Pro ABCA4 p.Asp523Glu ABCA4 p.Ser1071Leu ABCA4 p.Asp1204Asn ABCA4 p.Lys2056* ABCA4 p.Arg1843Trp ABCA4 p.Gly1439Asp 2 0071GrA R24H 1 19 2894ArG N965S 3 36 5196ϩ1GrA Splice 2 3 0161GrA C54Y 1 21 3113CrT A1038V 16 5196ϩ2TrC Splice 1 0179CrT A60V 1 22 3211insGT FS 1 37 5281del9 PAL1761del 1 0203CrG P68R 1 3212CrT S1071L 1 38 5459GrC R1820P 1 0223TrG C75G 1 3215TrC V1072A 1 39 5512CrT H1838Y 1 6 0634CrT R212C 1 3259GrA E1087K 1 5527CrT R1843W 1 0664del13 FS 1 3322CrT R1108C 6 40 5585-1GrA Splice 1 0746ArG D249G 1 23 3364GrA E1122K 1 5657GrA G1886E 1 8 1007CrG S336C 1 3385GrT R1129C 1 5693GrA R1898H 4 1018TrG Y340D 1 3386GrT R1129L 2 5714ϩ5GrA Splice 8 11 1411GrA E471K 1 24 3602TrG L1201R 1 42 5882GrA G1961E 16 12 1569TrG D523E 1 25 3610GrA D1204N 1 5898ϩ1GrT Splice 3 1622TrC L541P 1 28 4139CrT P1380L 4 43 5908CrT L1970F 1 1715GrA R572Q 2 4216CrT H1406Y 1 5929GrA G1977S 1 1715GrC R572P 1 4222TrC W1408R 4 6005ϩ1GrT Splice 1 13 1804CrT R602W 1 4232insTATG FS 1 44 6079CrT L2027F 11 1822TrA F608I 2 4253ϩ5GrT Splice 1 6088CrT R2030X 1 1917CrA Y639X 1 29 4297GrA V1433I 1 6089GrA R2030Q 1 1933GrA D645N 1 4316GrA G1439D 2 6112CrT R2038W 1 14 2005delAT FS 1 4319TrC F1440S 1 45 6148GrC V2050L 2 2090GrA W697X 1 4346GrA W1449X 1 6166ArT K2056X 1 2160ϩ1GrC Splice 1 30a 4462TrC C1488R 2 6229CrT R2077W 1 16 2453GrA G818E 1 4457CrT P1486L 1 46 6286GrA E2096K 1 2461TrA W821R 1 30b 4469GrA C1490Y 3 6316CrT R2106C 1 2536GrC D846H 1 4539ϩ1GrT Splice 1 47 6391GrA E2131K 1 2552GrC G851D 1 31 4577CrT T1526M 7 6415CrT R2139W 1 17 2588GrC G863A 11 4594GrA D1532N 3 6445CrT R2149X 1 19 2791GrA V931M 2 35 4947delC FS 1 48 6543del36 1181del12 1 2827CrT R943W 1 36 5041del15 VVAIC1681del 2 6709insG FS 1 2884delC FS 1 5087GrA S1696N 1 NOTE.-FS ϭ frameshift. Login to comment 77 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala ABCA4 p.Arg212Cys ABCA4 p.Leu541Pro ABCA4 p.Leu1970Phe ABCA4 p.Gly1977Ser ABCA4 p.Cys1488Arg ABCA4 p.Cys54Tyr ABCA4 p.Cys1490Tyr ABCA4 p.Cys75Gly ABCA4 p.Arg2139Trp ABCA4 p.Arg2149* ABCA4 p.Arg602Trp ABCA4 p.Asn965Ser ABCA4 p.Val2050Leu ABCA4 p.Glu2131Lys ABCA4 p.Arg2106Cys ABCA4 p.Arg2038Trp ABCA4 p.Arg2030* ABCA4 p.Leu2027Phe ABCA4 p.Pro68Arg ABCA4 p.Thr1526Met ABCA4 p.Arg1108Cys ABCA4 p.Arg2030Gln ABCA4 p.Trp821Arg ABCA4 p.Pro1380Leu ABCA4 p.Pro1486Leu ABCA4 p.Arg1898His ABCA4 p.Leu1201Arg ABCA4 p.Glu1087Lys ABCA4 p.Val931Met ABCA4 p.Phe1440Ser ABCA4 p.Trp1408Arg ABCA4 p.Ser1696Asn ABCA4 p.Arg1129Leu ABCA4 p.Arg2077Trp ABCA4 p.Phe608Ile ABCA4 p.Glu471Lys ABCA4 p.Glu1122Lys ABCA4 p.Glu2096Lys ABCA4 p.Val1433Ile ABCA4 p.Asp1532Asn ABCA4 p.Gly818Glu ABCA4 p.Gly1886Glu ABCA4 p.Asp645Asn ABCA4 p.His1838Tyr ABCA4 p.Arg572Gln ABCA4 p.Tyr639* ABCA4 p.Ala60Val ABCA4 p.Trp697* ABCA4 p.Ser336Cys ABCA4 p.Asp846His ABCA4 p.His1406Tyr ABCA4 p.Arg24His ABCA4 p.Arg943Trp ABCA4 p.Arg1129Cys ABCA4 p.Asp249Gly ABCA4 p.Gly851Asp ABCA4 p.Val1072Ala ABCA4 p.Tyr340Asp ABCA4 p.Arg572Pro ABCA4 p.Trp1449* ABCA4 p.Arg1820Pro ABCA4 p.Asp523Glu ABCA4 p.Ser1071Leu ABCA4 p.Asp1204Asn ABCA4 p.Lys2056* ABCA4 p.Arg1843Trp ABCA4 p.Gly1439Asp 2 0071GrA R24H 1 19 2894ArG N965S 3 36 5196af9;1GrA Splice 2 3 0161GrA C54Y 1 21 3113CrT A1038V 16 5196af9;2TrC Splice 1 0179CrT A60V 1 22 3211insGT FS 1 37 5281del9 PAL1761del 1 0203CrG P68R 1 3212CrT S1071L 1 38 5459GrC R1820P 1 0223TrG C75G 1 3215TrC V1072A 1 39 5512CrT H1838Y 1 6 0634CrT R212C 1 3259GrA E1087K 1 5527CrT R1843W 1 0664del13 FS 1 3322CrT R1108C 6 40 5585afa;1GrA Splice 1 0746ArG D249G 1 23 3364GrA E1122K 1 5657GrA G1886E 1 8 1007CrG S336C 1 3385GrT R1129C 1 5693GrA R1898H 4 1018TrG Y340D 1 3386GrT R1129L 2 5714af9;5GrA Splice 8 11 1411GrA E471K 1 24 3602TrG L1201R 1 42 5882GrA G1961E 16 12 1569TrG D523E 1 25 3610GrA D1204N 1 5898af9;1GrT Splice 3 1622TrC L541P 1 28 4139CrT P1380L 4 43 5908CrT L1970F 1 1715GrA R572Q 2 4216CrT H1406Y 1 5929GrA G1977S 1 1715GrC R572P 1 4222TrC W1408R 4 6005af9;1GrT Splice 1 13 1804CrT R602W 1 4232insTATG FS 1 44 6079CrT L2027F 11 1822TrA F608I 2 4253af9;5GrT Splice 1 6088CrT R2030X 1 1917CrA Y639X 1 29 4297GrA V1433I 1 6089GrA R2030Q 1 1933GrA D645N 1 4316GrA G1439D 2 6112CrT R2038W 1 14 2005delAT FS 1 4319TrC F1440S 1 45 6148GrC V2050L 2 2090GrA W697X 1 4346GrA W1449X 1 6166ArT K2056X 1 2160af9;1GrC Splice 1 30a 4462TrC C1488R 2 6229CrT R2077W 1 16 2453GrA G818E 1 4457CrT P1486L 1 46 6286GrA E2096K 1 2461TrA W821R 1 30b 4469GrA C1490Y 3 6316CrT R2106C 1 2536GrC D846H 1 4539af9;1GrT Splice 1 47 6391GrA E2131K 1 2552GrC G851D 1 31 4577CrT T1526M 7 6415CrT R2139W 1 17 2588GrC G863A 11 4594GrA D1532N 3 6445CrT R2149X 1 19 2791GrA V931M 2 35 4947delC FS 1 48 6543del36 1181del12 1 2827CrT R943W 1 36 5041del15 VVAIC1681del 2 6709insG FS 1 2884delC FS 1 5087GrA S1696N 1 NOTE.-FS afd; frameshift. Login to comment 101 ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Leu541Pro ABCA4 p.Val2050Leu ABCA4 p.Glu2131Lys ABCA4 p.Leu2027Phe ABCA4 p.Arg1898His ABCA4 p.Arg1898His ABCA4 p.Arg1898His ABCA4 p.Glu471Lys ABCA4 p.Arg572Gln ABCA4 p.Arg572Gln ABCA4 p.His1406Tyr ABCA4 p.Asp249Gly ABCA4 p.Tyr340Asp ABCA4 p.Asp1204Asn For the double-mutant chromosomes in the compound heterozygous families (AR31: Y340D and R572Q; AR106: E471K and E2131K; AR128: R572Q and G863A; and AR189: L541P and A1038V) and in those families in which the second disease chromosome was not identified (AR215: H1406Y and V2050L; AR264: D1204N and L2027F; AR254: D249G and R1898H; AR265: G863A and R1898H; AR285: 2714ϩ5GrA and 2884delC; and AR305: G863A and R1898H), in three cases (AR128, AR265, and AR305) each mutation on the double-mutant chromosome had been identified independently as disease causing in other, unrelated families with STGD1 (table 1). Login to comment 102 ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Leu541Pro ABCA4 p.Val2050Leu ABCA4 p.Glu2131Lys ABCA4 p.Leu2027Phe ABCA4 p.Arg1898His ABCA4 p.Arg1898His ABCA4 p.Arg1898His ABCA4 p.Glu471Lys ABCA4 p.Arg572Gln ABCA4 p.Arg572Gln ABCA4 p.His1406Tyr ABCA4 p.Asp249Gly ABCA4 p.Tyr340Asp ABCA4 p.Asp1204Asn For the double-mutant chromosomes in the compound heterozygous families (AR31: Y340D and R572Q; AR106: E471K and E2131K; AR128: R572Q and G863A; and AR189: L541P and A1038V) and in those families in which the second disease chromosome was not identified (AR215: H1406Y and V2050L; AR264: D1204N and L2027F; AR254: D249G and R1898H; AR265: G863A and R1898H; AR285: 2714af9;5GrA and 2884delC; and AR305: G863A and R1898H), in three cases (AR128, AR265, and AR305) each mutation on the double-mutant chromosome had been identified independently as disease causing in other, unrelated families with STGD1 (table 1). Login to comment 105 ABCA4 p.Val931Met ABCA4 p.Gly1439Asp Three (AR293, KKESH71, and KKESH214) of these 53 families were identical by descent for polymorphic markers flanking the ABCR mutations and had the same mutation (VVAIC1681del, G1439D, and V931M, respectively) segregating on each disease chromosome. Login to comment 106 ABCA4 p.Val931Met ABCA4 p.Gly1439Asp Three (AR293, KKESH71, and KKESH214) of these 53 families were identical by descent for polymorphic markers flanking the ABCR mutations and had the same mutation (VVAIC1681del, G1439D, and V931M, respectively) segregating on each disease chromosome. Login to comment 110 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala ABCA4 p.Leu2027Phe ABCA4 p.Thr1526Met ABCA4 p.Arg1108Cys Seven mutant alleles, including six missense amino acid substitutions and one splice-site mutation (G863A, A1038V, R1108C, T1526M, G1961E, L2027F, and 5714ϩ5GrA) accounted for 41% of the disease-causing mutations identified in this cohort. Login to comment 111 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala ABCA4 p.Arg2030* ABCA4 p.Leu2027Phe ABCA4 p.Thr1526Met ABCA4 p.Arg1108Cys ABCA4 p.Arg2030Gln ABCA4 p.Arg1129Leu ABCA4 p.Arg572Gln ABCA4 p.Arg1129Cys ABCA4 p.Arg572Pro In three instances, identical codons were affected by different base-pair substitutions, yielding different predicted missense amino acid substitutions (R572Q and R572P; R1129C and R1129L) or a missense substitution and a stop codon (R2030Q and R2030X). Login to comment 112 ABCA4 p.Arg2030* ABCA4 p.Arg2030Gln ABCA4 p.Arg1129Leu ABCA4 p.Arg572Gln ABCA4 p.Arg1129Cys ABCA4 p.Arg572Pro In three instances, identical codons were affected by different base-pair substitutions, yielding different predicted missense amino acid substitutions (R572Q and R572P; R1129C and R1129L) or a missense substitution and a stop codon (R2030Q and R2030X). Login to comment 139 ABCA4 p.Ala1038Val ABCA4 p.Leu2027Phe ABCA4 p.Thr1526Met ABCA4 p.Arg1108Cys Different families with the same combination of alleles (e.g., AR326 and AR391, both with genotype L2027F/T1526M; AR376 and AR393, both with genotype A1038V/R1108C) usually have similar ages at onset, as was shown for Figure 4 Pedigree AR33, a family with STGD that manifests a pseudodominant inheritance pattern. Login to comment 140 ABCA4 p.Ala1038Val ABCA4 p.Leu2027Phe ABCA4 p.Thr1526Met ABCA4 p.Arg1108Cys Different families with the same combination of alleles (e.g., AR326 and AR391, both with genotype L2027F/T1526M; AR376 and AR393, both with genotype A1038V/R1108C) usually have similar ages at onset, as was shown for Figure 4 Pedigree AR33, a family with STGD that manifests a pseudodominant inheritance pattern. Login to comment 146 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val However, variation in self-reported age at onset, even by 11 decade, was noted for two families with identical ABCR compound heterozygous genotypes (age 8 years for family AR417 and age 20 years for family AR274, each with genotype G1961E/A1038V), suggesting either modifier alleles or environmental factors affecting disease expression or different sensitivity to reported age at onset. Login to comment 147 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val However, variation in self-reported age at onset, even by 11 decade, was noted for two families with identical ABCR compound heterozygous genotypes (age 8 years for family AR417 and age 20 years for family AR274, each with genotype G1961E/A1038V), suggesting either modifier alleles or environmental factors affecting disease expression or different sensitivity to reported age at onset. Login to comment 148 ABCA4 p.Trp821Arg ABCA4 p.Pro1380Leu ABCA4 p.Pro1380Leu ABCA4 p.Glu1122Lys Individual AR534-05, with genotype P1380L/ W821R, presented with visual impairment at age 10 years, whereas his cousins, each with genotype P1380L/ E1122K, had onset of visual impairment at ages 8-10 years. Login to comment 149 ABCA4 p.Trp821Arg ABCA4 p.Pro1380Leu ABCA4 p.Pro1380Leu ABCA4 p.Pro1380Leu ABCA4 p.Trp1408Arg ABCA4 p.Phe608Ile ABCA4 p.Glu1122Lys ABCA4 p.Asp645Asn Two compound heterozygous families, AR335 and AR341, had both mutations in the same exon (F608I/D645N in exon 13 and P1380L/W1408R in exon 28, respectively) and had an early age at onset of 6 years. Login to comment 150 ABCA4 p.Pro1380Leu ABCA4 p.Trp1408Arg ABCA4 p.Phe608Ile ABCA4 p.Asp645Asn Two compound heterozygous families, AR335 and AR341, had both mutations in the same exon (F608I/D645N in exon 13 and P1380L/W1408R in exon 28, respectively) and had an early age at onset of 6 years. Login to comment 178 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Leu1970Phe ABCA4 p.Cys1490Tyr ABCA4 p.Cys75Gly ABCA4 p.Arg2149* ABCA4 p.Arg602Trp ABCA4 p.Leu2027Phe ABCA4 p.Leu2027Phe ABCA4 p.Thr1526Met ABCA4 p.Thr1526Met ABCA4 p.Arg1108Cys ABCA4 p.Arg1108Cys ABCA4 p.Trp821Arg ABCA4 p.Pro1380Leu ABCA4 p.Arg1898His ABCA4 p.Trp1408Arg ABCA4 p.Glu1122Lys ABCA4 p.Asp1532Asn ABCA4 p.Tyr340Asp ABCA4 p.Arg572Pro ABCA4 p.Ser1071Leu Table 2 ABCR Allelic Series MUTATION(S) PEDIGREE AGE AT ONSET (YEARS) MEAN AGE AT ONSET ‫ע‬ SD (YEARS)Allele 1 Allele 2 G863A Y340D, R772Q AR31 8 19.6 ‫ע‬ 12.7 51961GrA AR307 10 A1038V AR290 16 5714ϩ5GrA AR314 25 5898ϩ1GrT AR336 39 A1038V R572P AR321 6 12.5 ‫ע‬ 6.9 S1071L AR358 6 L1970F AR428 6 5196ϩ2TrC AR71 7 G1961E AR417 8 L2027F AR181 9 R1898H AR78 14 G863A AR290 16 G1961E AR274 20 R1108C AR393 20 R1108C AR376 25 P1380L W1408R AR341 6 8.2 ‫ע‬ 1.5 E1122K AR534 8 2005delAT AR357 8 D1532N AR423 9 W821R AR534 10 G1961E A1038V AR417 8 14.3 ‫ע‬ 4.5 C75G AR427 12 C1490Y AR370 13 2160ϩ1GrC AR218 14 4253ϩ5GrT AR373 19 A1038V AR274 20 L2027F R602W AR88 9 13.0 ‫ע‬ 5.5 A1038V AR181 9 R2149X AR263 9 T1526M AR326 19 T1526M AR391 19 (70%) had onset in the first 2 decades of life, but 11 (16%) had onset in the 3d decade and 6 (9%) in the 4th decade. Login to comment 179 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala ABCA4 p.Gly863Ala ABCA4 p.Leu1970Phe ABCA4 p.Cys1490Tyr ABCA4 p.Cys75Gly ABCA4 p.Arg2149* ABCA4 p.Arg602Trp ABCA4 p.Leu2027Phe ABCA4 p.Leu2027Phe ABCA4 p.Thr1526Met ABCA4 p.Thr1526Met ABCA4 p.Arg1108Cys ABCA4 p.Arg1108Cys ABCA4 p.Trp821Arg ABCA4 p.Pro1380Leu ABCA4 p.Arg1898His ABCA4 p.Trp1408Arg ABCA4 p.Glu1122Lys ABCA4 p.Asp1532Asn ABCA4 p.Tyr340Asp ABCA4 p.Arg572Pro ABCA4 p.Ser1071Leu Table 2 ABCR Allelic Series MUTATION(S) PEDIGREE AGE AT ONSET (YEARS) MEAN AGE AT ONSET cf2; SD (YEARS) Allele 1 Allele 2 G863A Y340D, R772Q AR31 8 19.6 cf2; 12.7 51961GrA AR307 10 A1038V AR290 16 5714af9;5GrA AR314 25 5898af9;1GrT AR336 39 A1038V R572P AR321 6 12.5 cf2; 6.9 S1071L AR358 6 L1970F AR428 6 5196af9;2TrC AR71 7 G1961E AR417 8 L2027F AR181 9 R1898H AR78 14 G863A AR290 16 G1961E AR274 20 R1108C AR393 20 R1108C AR376 25 P1380L W1408R AR341 6 8.2 cf2; 1.5 E1122K AR534 8 2005delAT AR357 8 D1532N AR423 9 W821R AR534 10 G1961E A1038V AR417 8 14.3 cf2; 4.5 C75G AR427 12 C1490Y AR370 13 2160af9;1GrC AR218 14 4253af9;5GrT AR373 19 A1038V AR274 20 L2027F R602W AR88 9 13.0 cf2; 5.5 A1038V AR181 9 R2149X AR263 9 T1526M AR326 19 T1526M AR391 19 (70%) had onset in the first 2 decades of life, but 11 (16%) had onset in the 3d decade and 6 (9%) in the 4th decade. Login to comment 191 ABCA4 p.Gly1961Glu ABCA4 p.Arg1898His We reported previously that three AMD-associated ABCR variants (R1898H, G1961E, and 6519D11bp) (Allikmets et al. 1997a) had been identified in families with STGD1 (Allikmets et al. 1997b). Login to comment 192 ABCA4 p.Gly1961Glu ABCA4 p.Leu1970Phe ABCA4 p.Arg1898His ABCA4 p.Arg1129Leu ABCA4 p.Glu471Lys Interestingly, four other STGD1-causing ABCR mutations (E471K, R1129L, 5196ϩ1GrA, and L1970F) in these new families were documented previously as AMD-associated ABCR variants (Allikmets et al. 1997a). Login to comment 193 ABCA4 p.Gly1961Glu ABCA4 p.Leu1970Phe ABCA4 p.Arg1129Leu ABCA4 p.Glu471Lys Importantly, the G1961E allele, identified as one of the two most frequent variants in both the Utah and the Boston cohorts of AMD patients (Allikmets et al. 1997a), was also the most frequently identified ABCR mutant allele in our cohort of 150 families with STGD1. Login to comment 194 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu In 6 of the 16 families with STGD1 who had a G1961E disease chromosome, the other mutant allele also was identified; in all 16 cases, G1961E cosegregated with the disease. Thus, G1961E is a pathologic mutation and not a benign variant. Login to comment 195 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu In 6 of the 16 families with STGD1 who had a G1961E disease chromosome, the other mutant allele also was identified; in all 16 cases, G1961E cosegregated with the disease. Thus, G1961E is a pathologic mutation and not a benign variant. Login to comment