ABCMdb

PMID: 19265867

Passerini I, Sodi A, Giambene B, Mariottini A, Menchini U, Torricelli F
Novel mutations in of the ABCR gene in Italian patients with Stargardt disease.
Eye (Lond). 2010 Jan;24(1):158-64. Epub 2009 Mar 6., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCA4 p.Gly1961Glu Missense mutations represented the most frequent finding (59.2%); G1961E was the most common mutation and it was associated with phenotypes in various degrees of severity. Login to comment 57 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.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.Arg212Cys ABCA4 p.Arg212Cys ABCA4 p.Arg212Cys ABCA4 p.Arg212Cys ABCA4 p.Arg212Cys ABCA4 p.Arg212Cys ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Thr1019Met ABCA4 p.Thr1019Met ABCA4 p.Thr1019Met ABCA4 p.Thr1019Met ABCA4 p.Thr1019Met ABCA4 p.Thr1019Met ABCA4 p.Gln1332* ABCA4 p.Gln1332* ABCA4 p.Leu1970Phe ABCA4 p.Leu1970Phe ABCA4 p.Gly1977Ser ABCA4 p.Gly1977Ser ABCA4 p.Asn965Ser ABCA4 p.Asn965Ser ABCA4 p.Asn96Lys ABCA4 p.Arg2030* ABCA4 p.Arg2030* ABCA4 p.Asn96His ABCA4 p.Asn96His ABCA4 p.Arg653Cys ABCA4 p.Arg653Cys ABCA4 p.Arg1098Cys ABCA4 p.Arg1098Cys ABCA4 p.Leu2140Gln ABCA4 p.Leu2140Gln ABCA4 p.Leu2140Gln ABCA4 p.Leu2140Gln ABCA4 p.Val767Asp ABCA4 p.Val767Asp ABCA4 p.Val767Asp ABCA4 p.Ala1598Asp ABCA4 p.Ala1598Asp ABCA4 p.Ala1598Asp ABCA4 p.Ala1598Asp ABCA4 p.Ala1598Asp ABCA4 p.Ala1598Asp ABCA4 p.Thr1526Met ABCA4 p.Thr1526Met ABCA4 p.Arg1108Cys ABCA4 p.Arg1108Cys ABCA4 p.Arg1108Cys ABCA4 p.Trp821Arg ABCA4 p.Trp821Arg ABCA4 p.Pro1380Leu ABCA4 p.Pro1380Leu ABCA4 p.Leu1580Ser ABCA4 p.Leu1580Ser ABCA4 p.Glu1087Lys ABCA4 p.Glu1087Lys ABCA4 p.Val931Met ABCA4 p.Val931Met ABCA4 p.Gly172Ser ABCA4 p.Gly172Ser ABCA4 p.Ser1696Asn ABCA4 p.Ser1696Asn ABCA4 p.Arg572* ABCA4 p.Arg572* ABCA4 p.Leu1473Met ABCA4 p.Leu1473Met ABCA4 p.Leu2221Pro ABCA4 p.Glu616Lys ABCA4 p.Glu616Lys ABCA4 p.Glu2096Lys ABCA4 p.Glu2096Lys ABCA4 p.Thr977Pro ABCA4 p.Thr977Pro ABCA4 p.Met840Arg ABCA4 p.Ser1099* ABCA4 p.Ser1099* ABCA4 p.Pro68Leu ABCA4 p.Pro68Leu ABCA4 p.Pro68Leu ABCA4 p.Pro68Leu ABCA4 p.Pro68Leu ABCA4 p.Pro68Leu ABCA4 p.Val1433Ile ABCA4 p.Val1433Ile ABCA4 p.Gly1078Glu ABCA4 p.Gly1078Glu ABCA4 p.Trp700* ABCA4 p.Gly690Val ABCA4 p.Gly690Val ABCA4 p.Pro1484Ser ABCA4 p.Pro1484Ser ABCA4 p.Pro1484Ser ABCA4 p.Pro1484Ser ABCA4 p.Pro1484Ser ABCA4 p.Pro1484Ser ABCA4 p.Ile156Val ABCA4 p.Thr970Pro ABCA4 p.Thr970Pro ABCA4 p.Thr970Pro ABCA4 p.Asn415Lys ABCA4 p.Trp1479* ABCA4 p.Trp1479* ABCA4 p.Trp1479* ABCA4 p.Trp1479* ABCA4 p.Gly978Asp ABCA4 p.Gln21* ABCA4 p.Gln21* ABCA4 p.Cys1177* ABCA4 p.Cys1177* ABCA4 p.Cys1177* ABCA4 p.Cys1177* ABCA4 p.Phe1015Glu ABCA4 p.Phe1015Glu ABCA4 p.Phe1015Glu ABCA4 p.Trp1408* ABCA4 p.Arg1055Trp ABCA4 p.Arg1055Trp ABCA4 p.Lys2172Arg ABCA4 p.Lys2172Arg ABCA4 p.Trp1461* ABCA4 p.Trp1461* Table 2 Summary of the mutations identified in the ABCR gene in our series of STGD Italian patients Patient Allele 1 mutation Allele 2 mutation S 1 R212C T1019M S 8 V1433I V1433I S 21 A1598D A1598D S 33 N96K G978D S 56 A1598D G1961E S 70 R212C T1019M S 71 W700X WT S 74 6750delA V767D S 77 G1961E WT S 82 Q21X G1961E S 106 C1177X G1961E S 107 C1177X G1961E S 114 T970P-F1015E - S 115 T970P-F1015E - S 120 N415K G1961E S 162 324-327insT 324-327insT S 181 W1408X G1961E S 190 C1177X A1598D S 201 G1961E WT S 202 Q21X T970P-F1015E S 213 M840R G1961E S 231 WT WT S 236 C1177X G1961E S 237 WT WT S 241 V256 splice WT S 246 IVS6-1g4t R1108C S 260 L2221P 5109delG-I156V S 321 IVS9 þ 1G4C S1099X S 328 IVS42 þ 4delG IVS35 þ 2t4c S 346 E2096K WT S 347 IVS28 þ 5g4a WT S 353 P1484S-G1961E P68L S 354 P1484S-G1961E P68L S 355 P1484S-G1961E P68L S 360 G1961E 5961delGGAC S 364 IVS35 þ 2t4c G1961E S 365 L541P/A1038V G1961E S 377 IVS42 þ 4delG IVS35 þ 2t4c S 380 R653C WT S 413 R212C T1019M S 414 A1598D G1961E S 417 G1078E G1961E S 438 R1055W WT S 440 4021ins24bp T1526M-G1961E S 449 W1479X L2140Q S 450 W1479X L2140Q S 474 W1461X G 1977S S 486 WT WT S 492 R1098C/L1970F 6548insTGAA S 528 T977P IVS40 þ 5g4a S 531 G690V Q1332X S 532 R572X L1473M-4733delGTTT S 535 IVS40 þ 5g4a 5917delG S 550 IVS40 þ 5g4a 6750delA S 555 250insCAAA WT S 556 250insCAAA WT S 575 N96H G1961E S 590 W821R IVS40 þ 5g4a S 592 V931M R1108C S 593 V767D R2030X Table 2 (Continued ) Patient Allele 1 mutation Allele 2 mutation S 594 G172S G1961E S 602 P1380L G1961E S 607 E616K L1580S-K2172R S 640 250insCAAA S1696N S 694 IVS35 þ 2t4c G1961E S 725 IVS13 þ 1g4a Q1376 splice S 731 L541P-A1038V G1961E S 755 N965S IVS40 e; 5g4a S 789 E1087K G1977S S 968 T1019M G1961E S 992 R212C G1961E Bold values indicate novel mutations. Login to comment 59 ABCA4 p.Ala1598Asp ABCA4 p.Val1433Ile The majority of patients (42/71, 59.1%) were compound heterozygotes for two missense mutations or one nonsense and one missense mutations, and 12 patients (16.9%) were simple heterozygotes. Only three patients were found to be homozygous for ABCR variants (324-327insT, V1433I, and A1598D). Login to comment 62 ABCA4 p.Gly1961Glu G1961E was the most common mutated allele among our STGD patients of Italian origin. Login to comment 83 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Arg212His ABCA4 p.Arg212His ABCA4 p.Asn1868Ile ABCA4 p.Asn1868Ile ABCA4 p.Arg943Gln ABCA4 p.Arg943Gln ABCA4 p.His423Arg ABCA4 p.His423Arg ABCA4 p.Ser2255Ile ABCA4 p.Ser2255Ile In our series, mainly consisting of patients coming from central Italy, G1961E was the most common mutant allele, in congruence with other studies performed in distinct dissimilar European populations.9,20 Nevertheless, the frequency of G1961E mutation (20.4% of our STGD alleles) was higher than in the other Italian Table 3 Summary of the polymorphic variants identified in the ABCR gene in our series of STGD Italian patients Location Polymorphic variants Number of alleles Exon 3 IVS3 þ 26a4g 14 Exon 5 D159 1 Exon 6 R212H 6 Exon 7 IVS7-32t4c 9 Exon 10 H423R 12 Exon 13 D644 1 Exon 14 IVS14 þ 50t4c 1 Exon 15 IVS15-13t4c 2 Exon 16 IVS16-13c4t 1 Exon 19 R943Q 3 Exon 20 L1988 1 Exon 23 Q1169 4 Exon 23 IVS23 þ 25g4a 2 Exon 24 T1176 6 Exon 24 K1182 3 Exon 28 P1401 1 Exon 33 IVS33-39t4c 2 Exon 34 IVS34 þ 16insgtt 4 Exon 38 D1817Q 7 Exon 40 N1868I 3 Exon 40 L1894 16 Exon 41 L1938 15 Exon 42 P1948 23 Exon 44 I2023 5 Exon 44 IVS44-16g4a 5 Exon 44 IVS44 þ 77g4a 1 Exon 45 I2083 5 Exon 46 D2095 19 Exon 48 IVS48 þ 21c4t 3 Exon 49 S2255I 5 studies where this mutation was detected in 11.110 and 9.7% 11 of the screened alleles. Login to comment 84 ABCA4 p.Gly1961Glu In earlier reports, G1961E was considered a mutation with a low pathogenetic influence,10,13 but in our series, it may be associated with STGD phenotypes of a varying severity. Login to comment 85 ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Leu541Pro Therefore, it can be speculated that its clinical expression depends on the mutation severity on the fellow allele, as suggested by earlier genotype/ phenotype studies.17,21 Still, although the A1038V mutation is commonly reported in the literature,9,13,27 in our series, it was detected in only two patients (1.4% of the patients, 0.7% of the alleles) within the L541P-A1038V complex allele. Login to comment