ABCMdb

PMID: 19365591

Maia-Lopes S, Aguirre-Lamban J, Castelo-Branco M, Riveiro-Alvarez R, Ayuso C, Silva ED
ABCA4 mutations in Portuguese Stargardt patients: identification of new mutations and their phenotypic analysis.
Mol Vis. 2009;15:584-91. Epub 2009 Mar 25., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCA4 p.Met1Thr We report the presence of 22 putative pathogenic alterations, including two sequence changes not found in other populations, c.2T>C (p.Met1Thr) and c.4036_4037delAC (p.Thr1346fs), and two novel disease-associated variants, c.400C>T (p.Gln134X) and c.4720G>T (p.Glu1574X). Login to comment 8 ABCA4 p.Leu11Pro The most prevalent pathologic variant was the missense mutation p.Leu11Pro. Login to comment 60 ABCA4 p.Ser1642Arg [Ser1642Arg]+[Val1681_Cys1685del], found in 9.5% of the families; p. Login to comment 61 ABCA4 p.Val931Met ABCA4 p.Ser1642Arg ABCA4 p.Ser1642Arg [Ser1642Arg]+[Val1681_Cys1685del], found in 9.5% of the families; p. Login to comment 62 ABCA4 p.Arg2030Gln ABCA4 p.Val931Met ABCA4 p.Ser1642Arg ABCA4 p.Met1Val [Val931Met]+[Ser1642Arg], found in 4.8% of the families, and p. Login to comment 63 ABCA4 p.Gly1961Glu ABCA4 p.Asn96Asp ABCA4 p.Leu2027Phe ABCA4 p.Arg2030Gln ABCA4 p.Arg2030Gln ABCA4 p.Val931Met ABCA4 p.Met1Val ABCA4 p.Met1Val ABCA4 p.Arg290Trp [Met1Val]+ [Arg2030Gln], found in 4.8% of the families (for details, see Table 1). Login to comment 64 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Leu11Pro ABCA4 p.Asn96Asp ABCA4 p.Leu2027Phe ABCA4 p.Arg2030Gln ABCA4 p.Val931Met ABCA4 p.Val931Met ABCA4 p.Ser1642Arg ABCA4 p.Met1Val ABCA4 p.Arg290Trp Most of the mutations detected have been reported as STGD-associated variants: p.Met1Val, p.Asn96Asp, p.Arg290Trp, p.Val931Met, p.Gly1961Glu, p.Leu2027Phe, p.Arg2030Gln, p.Asp1048fs, and IVS40+5G>A. Login to comment 65 ABCA4 p.Gly1961Glu ABCA4 p.Leu11Pro ABCA4 p.Val931Met ABCA4 p.Ser1642Arg Although most of the mutations were found in one family, five disease-associated alleles were detected in unrelated STGD families (p.Leu11Pro, p.Asp1048fs; p.Gly1961Glu; p.Ser1642Arg; p.Val1681_Cys1685del; p.Val931Met). Login to comment 67 ABCA4 p.Asn96Asp ABCA4 p.Asn96Asp ABCA4 p.Pro1380Leu ABCA4 p.Pro1380Leu Family Patient CFC Onset (age) VA (OD/OS) Nucleotide changes (exons) Effect changes [references] 1 4427 S 7 1/10 / 1/10 c.286A>G(3) / c.4139C>T(28) p.Asn96Asp [30]/p.Pro1380Leu [13] 4413 S 14 1/10 / 0.5/10 c.286A>G(3) / c.4139C>T(28) p.Asn96Asp [30]/p.Pro1380Leu [13] 4454 S 11 1/10 / 1/10 c.286A>G(3) / c. Login to comment 68 ABCA4 p.Arg602Trp ABCA4 p.Asn96Asp ABCA4 p.Asn96Asp ABCA4 p.Asn96Asp ABCA4 p.Pro1380Leu ABCA4 p.Pro1380Leu ABCA4 p.Pro1380Leu Family Patient CFC Onset (age) VA (OD/OS) Nucleotide changes (exons) Effect changes [references] 1 4427 S 7 1/10 / 1/10 c.286A>G(3) / c.4139C>T(28) p.Asn96Asp [30]/p.Pro1380Leu [13] 4413 S 14 1/10 / 0.5/10 c.286A>G(3) / c.4139C>T(28) p.Asn96Asp [30]/p.Pro1380Leu [13] 4454 S 11 1/10 / 1/10 c.286A>G(3) / c. Login to comment 69 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Leu11Pro ABCA4 p.Arg602Trp ABCA4 p.Asn96Asp ABCA4 p.Leu2027Phe ABCA4 p.Arg2030Gln ABCA4 p.Pro1380Leu ABCA4 p.Leu1201Arg ABCA4 p.Arg290Trp 4139C>T(28) p.Asn96Asp [30]/p.Pro1380Leu [13] 2 4458 Mi 5 8/10 / 6/10 ND / ND ND/ND 4455 S 8 1/10 / 8/10 ND / ND ND/ND 3 4431 Mo 6 1,6/10 / 1,6/10 c.1804C>T(13) / c.IVS+5G>A(40) p.Arg602Trp [30]/SPLICE [11] 4 4626 S 6 FC / FC c.3211_3212insGT(22) / c.3211_3212insGT(22) p.Asp1048fs [5]/p.Asp1048fs [5] 5 4514 S 12 1/10 / 1/10 c.32T>C(1) / c. Login to comment 70 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Leu11Pro ABCA4 p.Leu2027Phe ABCA4 p.Arg2030Gln ABCA4 p.Leu1201Arg ABCA4 p.Arg290Trp [1A>G(1)]+[6089G>A(44)] p.Leu11Pro [12]/p.(Met1Val [6])+(Arg2030Gln [9]) 6 4525 Mo 14 1/10 / 1/10 ND / c.868C>T(8) ND/p.Arg290Trp [6] 7 4585 Mo 11 0.5/10 / 0.5/10 c.6079C>T(44) / ND p.Leu2027Phe [5]/ND 8 4678 Mo 9 0.5/10 / 1/10 c.3113C>T(21) / c.3602T>G(24) p.Ala1038Val [5]/p.Leu1201Arg [9] 9 4675 Mo 7 0.5/10 / 1/10 c.2T<C(1) / c.2T<C(1) p.Met1Thr/p.Met1Thr 10 4737 Mo 24 1.2/10 / 1.2/10 c.5882G>A(42) / c.3211_3212insGT(22) p.Gly1961Glu [4]/p.Asp1048fs 11 4613 S 9 FC / FC c. Login to comment 71 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Leu11Pro ABCA4 p.Val931Met ABCA4 p.Ser1642Arg (Ser1642Arg [10])+(Val1681_Cys1685del [10])/ p.Leu11Pro 12 4796 Mo 43 1/10 / 3/10 c.4720G>T(33) / c.2791G>A(19) p.Glu1574X/p.Val931Met [5] 13 4859 Mo 30 0.5/10 / 0.5/10 c.5882G>A(42) / ND p.Gly1961Glu/ND 5472 Mo 30 6/10 / 8/10 c.5882G>A(42) / ND p.Gly1961Glu/ND 14 4974 S 7 1/10 / 1/10 c.4036_4037delAC(27) / c.400C>T(4) p.Thr1346fs/p.Gln134X 4975 S 7 1/10 / 1/10 c. Login to comment 72 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Leu11Pro ABCA4 p.Leu11Pro ABCA4 p.Leu11Pro ABCA4 p.Val643Gly ABCA4 p.Val931Met ABCA4 p.Ser1642Arg ABCA4 p.Arg602Thr (Ser1642Arg [10])+(Val1681_Cys1685del [10])/ p.Leu11Pro 12 4796 Mo 43 1/10 / 3/10 c.4720G>T(33) / c.2791G>A(19) p.Glu1574X/p.Val931Met [5] 13 4859 Mo 30 0.5/10 / 0.5/10 c.5882G>A(42) / ND p.Gly1961Glu/ND 5472 Mo 30 6/10 / 8/10 c.5882G>A(42) / ND p.Gly1961Glu/ND 14 4974 S 7 1/10 / 1/10 c.4036_4037delAC(27) / c.400C>T(4) p.Thr1346fs/p.Gln134X 4975 S 7 1/10 / 1/10 c. Login to comment 73 ABCA4 p.Leu11Pro ABCA4 p.Leu11Pro ABCA4 p.Val643Gly ABCA4 p.Arg602Thr 4036_4037delAC(27) / c.400C>T(4) p.Thr1346fs/p.Gln134X 15 5193 Mo 9 1/10 / 1/10 ND / ND ND/ND 16 5138 Mo 27 1/10 / 1/10 ND / ND ND/ND 17 5111 Mo 29 2.5/10 / 1.6/10 c.1928T>G(13) / ND p.Val643Gly/ND 5137 Mo 25 3/10 / FC ND / c.32T>C(1) ND/p.Leu11Pro 18 5709 Mi 9 2/10 / 2/10 c.32T>C(1) / c.1804C<T(13) p.Leu11Pro/p.Arg602Thr [9] 19 5434 Mo 17 2/10 / 2/10 c. Login to comment 75 ABCA4 p.Val931Met ABCA4 p.Ser1642Arg [Val931Met]+[Ser1642Arg]/ p. Login to comment 76 ABCA4 p.Val931Met ABCA4 p.Ser1642Arg ABCA4 p.Ser1642Arg [Val931Met]+[Ser1642Arg]/ p. Login to comment 77 ABCA4 p.Ser1642Arg [Ser1642Arg]+ [Val1681_Cys1685del] 20 5689 Mi 1 1/10 / 1/10 ND / ND ND/ND 21 5917 Mi 9 0.5/10 / 2/10 ND / ND ND/ND The translation start codon ATG/methionine is numbered +1. Login to comment 80 ABCA4 p.Leu11Pro most prevalent disease-associated variant was the missense mutation p.Leu11Pro, accounting for 11% (4/36) of the disease chromosomes. Login to comment 81 ABCA4 p.Leu11Pro most prevalent disease-associated variant was the missense mutation p.Leu11Pro, accounting for 11% (4/36) of the disease chromosomes. Login to comment 82 ABCA4 p.Gly1961Glu The p.Gly1961Glu mutation, associated with AMD, was found in 9.5% of our patients. Login to comment 83 ABCA4 p.Gly1961Glu The p.Gly1961Glu mutation, associated with AMD, was found in 9.5% of our patients. Login to comment 89 ABCA4 p.Val931Met The STGD patient from Family 12 is a compound heterozygous with p.Val931Met and a novel nonsense mutation at exon 33 (p.Glu1574X; Figure 1B). Login to comment 90 ABCA4 p.Val931Met The STGD patient from Family 12 is a compound heterozygous with p.Val931Met and a novel nonsense mutation at exon 33 (p.Glu1574X; Figure 1B). Login to comment 103 ABCA4 p.Met1Thr Pedigrees, elution dHPLC profiles, and sequence changes for each new disease-associated ABCA4 mutations are shown: A - p.Met1Thr (c. Login to comment 104 ABCA4 p.Met1Thr Pedigrees, elution dHPLC profiles, and sequence changes for each new disease-associated ABCA4 mutations are shown: A - p.Met1Thr (c. Login to comment 110 ABCA4 p.Arg212His ABCA4 p.Asn1868Ile ABCA4 p.Pro1948Leu ABCA4 p.Arg943Gln ABCA4 p.His423Arg ABCA4 p.Ser2255Ile Exon Nucleotide Change Effect STGD Families Frequency References IVS3 c.302+20C>T - 12 4.8% [6] IVS3 c.302+26A>G - 7,12,13,14 1.91% [6] 6 c.635G>A p.Arg212His 13,19 9.5% [15] IVS7 c.859+8T>C - 17 4.8% Present study 10 c.1268A>G p.His423Arg 2,4,5,6,10,11,12,13,14,18,19 53% [13] 10 c.1269C>T p.His423His 16 4.8% [13] IVS10 c.1356+5delG SPLICE 1,7,11,15,20 23.8% [13] IVS14 c.2161+47T>C - 18 4.8% Present study 19 c.2828G>A p.Arg943Gln 3,10,18,19 19.1% [5] IVS19 c.2919+34C>T - 12 4.8% Present study 20 c.2964T>C p.Leu988Leu 12 4.8% [6] IVS22 c.3326-19G>A - 2 4.8% Present study IVS33 c.4773+48C>T Splice 1,2,3,5,6,8,9,10,12,13,14,16,17,18,19,20 76.2% [13] 40 c.5603A>T p.Asn1868Ile 4,10,17 14.3% [6] 40 c.5682G>C p.Leu1894Leu 1,2,4,5,8,10,12,13,17,18 47.6% [6] 41 c.5814A>G p.Leu1938Leu 1,2,5,8,10,12,13,18 3.81% [6] 42 c.5843CA>TG/c.5843C>T p.Pro1948Leu 11 4.8% [14] 42 c.5844A>G p.Pro1948Pro 1,2,5,8,10,12,13 33.3% [14] 44 c.6069C>T p.Ile2023Ile 9,12,14,19 19.1% [6] 45 c.6249C>T p.Ile2083Ile 9,12,14,19 19.1% [5] 46 c.6285T>C p.Asp2095Asp 1,2,8,9,10,12,14,19 38.1% [14] IVS48 c.6769+21C>T SPLICE 1,10 9.5% [6] 49 c.6764G>T p.Ser2255Ile 1,9,14,19 19.1% [5] Several polymorphisms in exons and introns (IVS) throughout the entire ABCA4 gene were found in our study population. Login to comment 111 ABCA4 p.Arg212His ABCA4 p.Asn1868Ile ABCA4 p.Pro1948Leu ABCA4 p.Arg943Gln ABCA4 p.His423Arg ABCA4 p.Ser2255Ile Exon Nucleotide Change Effect STGD Families Frequency References IVS3 c.302+20C>T - 12 4.8% [6] IVS3 c.302+26A>G - 7,12,13,14 1.91% [6] 6 c.635G>A p.Arg212His 13,19 9.5% [15] IVS7 c.859+8T>C - 17 4.8% Present study 10 c.1268A>G p.His423Arg 2,4,5,6,10,11,12,13,14,18,19 53% [13] 10 c.1269C>T p.His423His 16 4.8% [13] IVS10 c.1356+5delG SPLICE 1,7,11,15,20 23.8% [13] IVS14 c.2161+47T>C - 18 4.8% Present study 19 c.2828G>A p.Arg943Gln 3,10,18,19 19.1% [5] IVS19 c.2919+34C>T - 12 4.8% Present study 20 c.2964T>C p.Leu988Leu 12 4.8% [6] IVS22 c.3326-19G>A - 2 4.8% Present study IVS33 c.4773+48C>T Splice 1,2,3,5,6,8,9,10,12,13,14,16,17,18,19,20 76.2% [13] 40 c.5603A>T p.Asn1868Ile 4,10,17 14.3% [6] 40 c.5682G>C p.Leu1894Leu 1,2,4,5,8,10,12,13,17,18 47.6% [6] 41 c.5814A>G p.Leu1938Leu 1,2,5,8,10,12,13,18 3.81% [6] 42 c.5843CA>TG/c.5843C>T p.Pro1948Leu 11 4.8% [14] 42 c.5844A>G p.Pro1948Pro 1,2,5,8,10,12,13 33.3% [14] 44 c.6069C>T p.Ile2023Ile 9,12,14,19 19.1% [6] 45 c.6249C>T p.Ile2083Ile 9,12,14,19 19.1% [5] 46 c.6285T>C p.Asp2095Asp 1,2,8,9,10,12,14,19 38.1% [14] IVS48 c.6769+21C>T SPLICE 1,10 9.5% [6] 49 c.6764G>T p.Ser2255Ile 1,9,14,19 19.1% [5] Several polymorphisms in exons and introns (IVS) throughout the entire ABCA4 gene were found in our study population. 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