ABCMdb

PMID: 10958763

Rivera A, White K, Stohr H, Steiner K, Hemmrich N, Grimm T, Jurklies B, Lorenz B, Scholl HP, Apfelstedt-Sylla E, Weber BH
A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration.
Am J Hum Genet. 2000 Oct;67(4):800-13. Epub 2000 Aug 24., [PubMed]

Sentences

No. Mutations Sentence Comment

7 ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro Eight different alleles account for 61% of the identified disease alleles, and at least one of these, the L541P-A1038V complex allele, appears to be a founder mutation in the German population. Login to comment 22 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala Certain mutant alleles-for example, G863A, A1038V, and G1961E-appear to be more common and may have altered frequencies in different populations, as a result of founder effect (Maugeri et al. 1999; Simonelli et al. 2000). Login to comment 79 ABCA4 p.Asn1868Ile ABCA4 p.Arg152Gln ABCA4 p.Ala60Thr ABCA4 p.Ala60Glu ABCA4 p.Val1921Met Also considered pathological were missense mutations causing nonconservative amino acid changes-for example, A60T and A60E (table 2)-with the exception of those that were found at similar frequencies in the three study groups-for example, R152Q, N1868I, and V1921M (tables 3 and 4). Login to comment 80 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Arg212Cys ABCA4 p.Leu541Pro ABCA4 p.Gly1977Ser ABCA4 p.Arg1300* ABCA4 p.Tyr362* ABCA4 p.Arg653Cys ABCA4 p.Arg1443His ABCA4 p.Arg681* ABCA4 p.Trp855* ABCA4 p.Arg1108Cys ABCA4 p.Pro1380Leu ABCA4 p.Pro1486Leu ABCA4 p.Arg152* ABCA4 p.Thr901Ala ABCA4 p.Arg1898His ABCA4 p.Trp663* ABCA4 p.Thr959Ile ABCA4 p.Arg2077Trp ABCA4 p.Glu471Lys ABCA4 p.Pro68Leu ABCA4 p.Gly65Glu ABCA4 p.Gln1412* ABCA4 p.Gly1975Arg ABCA4 p.Glu1399Lys ABCA4 p.Gln1750* ABCA4 p.Ser1689Pro ABCA4 p.Cys1488Tyr ABCA4 p.Arg572Gln ABCA4 p.Cys230Ser ABCA4 p.Gly607Arg ABCA4 p.Tyr2203* ABCA4 p.Ser765Arg ABCA4 p.Arg1097Cys ABCA4 p.Cys764Tyr ABCA4 p.Ser1063Pro ABCA4 p.Gly1748Arg ABCA4 p.Gln635Lys ABCA4 p.Phe1440Val ABCA4 p.Glu1885Lys ABCA4 p.Arg1705Leu ABCA4 p.Asn247Ser ABCA4 p.Leu1763Pro ABCA4 p.Ala60Thr ABCA4 p.Ala60Glu ABCA4 p.Leu1430Pro ABCA4 p.Glu328Val ABCA4 p.His914Ala ABCA4 p.Met1733Thr ABCA4 p.Gly72Arg ABCA4 p.Gln635* ABCA4 p.Ala2216Val ABCA4 p.Glu1036Lys ABCA4 p.Glu1270* ABCA4 p.Thr1537Met ABCA4 p.Arg2077Gly 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. Login to comment 81 ABCA4 p.Gly863Ala b Effect is missense mutation (G863A) and in-frame deletion (delG863), according to Maugeri et al. (1999). Login to comment 82 ABCA4 p.Gly1961Glu ABCA4 p.Asp2177Asn ABCA4 p.Leu1970Phe ABCA4 p.Ile1562Thr ABCA4 p.Glu1087Asp ABCA4 p.Val552Ile ABCA4 p.Arg152Gln ABCA4 p.Gly2059Ala ABCA4 p.Leu2241Val ABCA4 p.Val1921Met Table 3 Rare Sequence Variants in the ABCA4 Gene EXON AND NUCLEOTIDE CHANGE EFFECT NO. OF ALLELES REFERENCE(S) STGD (288) AMD (400) Control (440) 5: 455GrA R152Q 3 1 3 This study 8: IVS8ϩ38ArT Unknown 0 1 0 This study 12: 1654GrA V552I 0 0 2 This study IVS11-6CrG Unknown 0 4 2 This study 13: 1932CrT D644D 2 0 0 This study 17: IVS16-12CrG Unknown 0 0 8 This study 18: IVS17-56CrG Unknown 3 0 0 This study IVS17-36CrT Unknown 0 2 1 This study 22: 3261ArC E1087D 1 0 0 This study 3264CrT P1088P 0 0 1 This study IVS21-20CrT Unknown 1 0 0 This study 23: IVS23ϩ10TrG Unknown 1 0 0 This study IVS23ϩ17GrC Unknown 1 0 0 This study 24: IVS23-28TrC Unknown 2 4 1 This study 25: 3759GrA T1253T 1 0 0 This study 28: 4140GrA P1380P 2 0 0 This study IVS28ϩ43GrA Unknown 4 3 1 This study 29: IVS29ϩ13GrA Unknown 0 1 0 This study IVS29ϩ32ArG Unknown 1 0 0 This study 31: 4578GrA T1526T 0 1 0 This study 32: IVS32ϩ45TrC Unknown 1 0 0 This study 33: IVS32-57TrG Unknown 0 0 1 This study 4685TrC I1562T 0 0 6 Allikmets et al. (1997b) 36: IVS36ϩ20GrA Unknown 1 0 0 This study 39: 5487GrT L1829L 0 0 1 This study IVS38-10TrC Unknown 9 0 0 Maugeri et al. (1999) 41: 5761GrA V1921M 1 1 1 This study 43: 5908CrT L1970F 1 0 1 Allikmets et al. (1997b), Rozet et al. (1998), Lewis et al. (1999) IVS43ϩ7ArC Unknown 1 0 0 This study 44: 6027CrT I2023I 1 0 0 Allikmets et al. (1997a), Nasonkin et al. (1998) 45: 6176GrC G2059A 0 0 1 This study 46: IVS46ϩ27GrA Unknown 0 0 1 This study 47: IVS46-46TrA Unknown 1 0 0 This study 48: IVS48ϩ21CrT Unknown 18a 2a 0 Allikmets et al. (1997b), Nasonkin et al. (1998), Papaioannou et al. (2000) 6529GrA D2177N 2 3 4 Allikmets et al. (1997b) 6721CrG L2241V 1 0 0 This study a Occurs together with G1961E in 17/18 and 2/2 instances. Login to comment 83 ABCA4 p.Arg212His ABCA4 p.Asn1868Ile ABCA4 p.Pro1948Leu ABCA4 p.Arg943Gln ABCA4 p.His423Arg Table 4 Polymorphisms in the ABCA4 Gene EXON AND NUCLEOTIDE CHANGE EFFECT NO. OF ALLELES REFERENCE(S) STGD (n p 288) AMD (n p 400) Control (n p 440) 6: 635GrA R212H 8 8 32 This study 7: IVS6-32TrC Unknown 53 115 130 This study 10: 1267ArG H423R 52 79 101 This study 1268CrT H423H 11 17 17 This study 14: IVS14ϩ50TrCa Unknown 22 18 9 This study 19: 2828GrAa R943Q 23 14 10 Allikmets et al. (1997a, 1997b), Maugeri et al. (1999), Papaioannou et al. (2000) 28: 4203CrA P1401P 29 13 20 Maugeri et al. (1999) 33: IVS32-38CrT Unknown 1 4 12 This study 34: IVS33-16delGT Unknown 24 8 12 This study 40: 5603ArT N1868I 37 40 46 Maugeri et al. (1999) 5682GrC L1894L 73 52 91 Maugeri et al. (1999), Papaioannou et al. (2000) 41: 5814ArG L1938L 50 68 70 This study 42: IVS41-11GrA Unknown 46 56 55 Maugeri et al. (1999) 5844ArG P1948P 40 40 39 Maugeri et al. (1999), Papaioannou et al. (2000) 5843CArTG P1948L 5 14 13 Maugeri et al. (1999) 44: IVS43-16GrA Unknown 46 48 55 Papaioannou et al. (2000) 45: IVS45ϩ7GrA Unknown 10 15 11 Papaioannou et al. (2000) 6249CrT I2083I 13 17 27 Allikmets et al. (1997a), Maugeri et al. (1999) 46: 6285TrC D2095D 38 36 33 Maugeri et al. (1999) a 2828GrA and IVS14ϩ50TrC occur on the same haplotype together with 2588GrC. Login to comment 90 ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro In the group with AMD, 400 chromosomes were studied and 19 mutations were identified, with L541P and A1038V occurring on a single haplotype in one patient (AMD43). Login to comment 100 ABCA4 p.Gly1961Glu because of linkage disequilibrium with the mutation G1961E (data not shown). Login to comment 101 ABCA4 p.Arg212His ABCA4 p.Asn1868Ile ABCA4 p.Pro1948Leu ABCA4 p.Arg943Gln ABCA4 p.His423Arg Nineteen different alterations were present in 11% of the control alleles and were classified as polymorphisms (table 4); these include five nonconservative amino acid substitutions (R212H, H423R, R943Q, N1868I, and P1948L). Login to comment 111 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu 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.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Arg212Cys ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Gly1977Ser ABCA4 p.Arg1300* ABCA4 p.Tyr362* ABCA4 p.Arg1443His ABCA4 p.Arg681* ABCA4 p.Arg681* ABCA4 p.Trp855* ABCA4 p.Arg1108Cys ABCA4 p.Arg1108Cys ABCA4 p.Arg1898His ABCA4 p.Arg1898His ABCA4 p.Arg1898His ABCA4 p.Trp663* ABCA4 p.Thr959Ile ABCA4 p.Arg2077Trp ABCA4 p.Glu471Lys ABCA4 p.Pro68Leu ABCA4 p.Gly65Glu ABCA4 p.Gln1412* ABCA4 p.Gln1412* ABCA4 p.Gln1412* ABCA4 p.Gly1975Arg ABCA4 p.Glu1399Lys ABCA4 p.Glu1399Lys ABCA4 p.Gln1750* ABCA4 p.Ser1689Pro ABCA4 p.Cys1488Tyr ABCA4 p.Arg572Gln ABCA4 p.Cys230Ser ABCA4 p.Gly607Arg ABCA4 p.Tyr2203* ABCA4 p.Tyr2203* ABCA4 p.Ser765Arg ABCA4 p.Arg1097Cys ABCA4 p.Cys764Tyr ABCA4 p.Ser1063Pro ABCA4 p.Gly1748Arg ABCA4 p.Gln635Lys ABCA4 p.Phe1440Val ABCA4 p.Glu1885Lys ABCA4 p.Arg1705Leu ABCA4 p.Ala60Thr ABCA4 p.Leu1430Pro ABCA4 p.Leu1430Pro 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. Login to comment 125 ABCA4 p.Arg1300* ABCA4 p.Tyr362* Two patients, STGD108 and STGD121, are heterozygous for both an alteration in the donor splice site of intron 40 (IVS40ϩ5GrA) and a nonsense mutation (STGD108, Y362X and STGD121, R1300X). Login to comment 142 ABCA4 p.Leu1970Phe ABCA4 p.Arg152Gln ABCA4 p.Val1921Met As well as changes not affecting the specificity of amino acid residues and conservative amino acid substitutions, included in the latter category are some rare nonconservative changes found in similar frequencies in the three study groups-for example, R152Q, V1921M, and L1970F. Login to comment 143 ABCA4 p.Asp2177Asn Under our definitions, the conservative amino acid alteration D2177N, which has been described elsewhere as associated with AMD (Allikmets et al. 1997a; Allikmets and the International ABCR Screening Consortium 2000), was also classified as a rare sequence variant. Login to comment 145 ABCA4 p.Ile1562Thr A notable finding is the high frequencies in the control group of two independent alterations, IVS16-12CrG (1.8%) and I1562T (1.4%), in contrast to their complete absence in the group with STGD as well as in the group with AMD. Login to comment 146 ABCA4 p.Ile1562Thr Although IVS16-12CrG has not been reported elsewhere, I1562T has been found two times in patients with AMD but not in those with STGD or in 220 controls (Allikmets et al. 1997a). Login to comment 149 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro Although the majority of mutations are rare, found in only one or two families, three disease alleles (2588GrC, L541P-A1038V, and G1961E) are present at high frequencies in the German population. Login to comment 150 ABCA4 p.Gly1961Glu The most frequent is G1961E, which represents 34 (20.5%) of 166 identified alleles, a frequency that is significantly higher than the 4%-9% reported in other studies (Allikmets 1997a; Lewis et al. 1999; Maugeri et al. 1999; Simonelli et al. 2000). Login to comment 152 ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro The second-most-frequent allele is a complex allele, with A1038V occurring on the same haplotype as L541P (21/166 [12.7%]). Login to comment 153 ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro Although the A1038V mutation is commonly reported in the literature, the L541P-A1038V complex allele has been reported only five times (Rozet et al. 1998; Fishman et al. 1999; Lewis et al. 1999; Maugeri et al. 1999). Login to comment 156 ABCA4 p.Ala1038Val ABCA4 p.Arg681* ABCA4 p.Arg1108Cys ABCA4 p.Arg1898His ABCA4 p.Gln1412* These three alterations, in combination with five others (R681X, A1038V as noncomplex allele, R1108C, Q1412X, R1898H, and IVS40ϩ5GrA), account for 61.4% of the detectable disease chromosomes in the German patients with STGD. Login to comment 172 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro On the contrary, specific mutations are associated with highly variable ages at onset; for example, compound heterozygosity for the complex allele L541P-A1038V and G1961E was found in patients with age at onset of 9-25 years (table 5). Login to comment 176 ABCA4 p.Arg1300* ABCA4 p.Tyr362* Two additional patients, STGD108 and STGD121, each have a truncating mutation (Y362X and R1300X) in combination with the splice-site mutation IVS40ϩ5GrA. Login to comment 182 ABCA4 p.Gly1961Glu ABCA4 p.Asp2177Asn This stands in contrast to a recentP p .72 study, involving 15 research groups from the United States and Europe, that specifically investigated the frequency of two common ABCA4 variants, G1961E and D2177N, in a large cohort (11,200 individuals each) of patients with AMD and of controls (Allikmets and The International ABCR Screening Consortium 2000). Login to comment 189 ABCA4 p.Ala1038Val ABCA4 p.Arg1898His The findings in this study point to additional variants (2588GrC, A1038V, and R1898H) that are present in reasonable frequencies in the German population and that may be worthwhile candidates for further extended analyses in large-scale international efforts. Login to comment