ABCMdb

PMID: 14517951

Jaakson K, Zernant J, Kulm M, Hutchinson A, Tonisson N, Glavac D, Ravnik-Glavac M, Hawlina M, Meltzer MR, Caruso RC, Testa F, Maugeri A, Hoyng CB, Gouras P, Simonelli F, Lewis RA, Lupski JR, Cremers FP, Allikmets R
Genotyping microarray (gene chip) for the ABCR (ABCA4) gene.
Hum Mutat. 2003 Nov;22(5):395-403., [PubMed]

Sentences

No. Mutations Sentence Comment

30 ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Gly863Ala What makes ABCR a more difficult diagnostic target than CFTR is that the most frequent disease-associated ABCR alleles, e.g., 5882G>A (G1961E), 2588G>C (G863A/ delG863), and 3113C>T (A1038V), have each been described in only B10% of STGD patients in a distinct population, whereas the delF508 allele of CFTR accounts for close to 70% of all cystic fibrosis alleles [Zielenski and Tsui, 1995]. Login to comment 69 ABCA4 p.Arg2077Trp B: Missense mutation R2077W in an Italian Stargardt patient, analyzed by Genoramat genotyping software. Login to comment 88 ABCA4 p.Arg212His ABCA4 p.Asn1868Ile ABCA4 p.Pro1948Leu ABCA4 p.Arg943Gln ABCA4 p.His423Arg ABCA4 p.Ser2255Ile Several common polymorphisms were also included, mainly from the coding region (R212H, H423R, R943Q, N1868I, P1948L, S2255I). Login to comment 101 ABCA4 p.Gly863Ala TABLE 1.Validation of theABCR400 Array^Comparison of the SSCP and Chip Data STGD patients Controls SSCP ABCR400 array ABCR400 array Chromosomes analyzed 272 272 192 Di¡erent disease-associated variants 72 96 8 Disease-associated alleles 155 215 9 Disease chromosomes (%) 149 (54.8%) 189 (69.5%) 9 (4.7%) Complex alleles 17 40 2 Complex alleles include 2588G4C;2828G4A (G863A;R943Q). Login to comment 102 ABCA4 p.Arg943Gln R943Q, as a frequent polymorphism, is not counted in the disease-associated alleles row. Login to comment 115 ABCA4 p.Gly1961Glu ABCA4 p.Gly863Ala ABCA4 p.Leu541Pro ABCA4 p.Arg1640Trp ABCA4 p.Cys1488Arg ABCA4 p.Cys54Tyr ABCA4 p.Cys1490Tyr ABCA4 p.Val989Ala ABCA4 p.Arg1443His ABCA4 p.Arg212His ABCA4 p.Arg681* ABCA4 p.Arg2030Gln ABCA4 p.Pro1380Leu ABCA4 p.Pro1486Leu ABCA4 p.Cys2150Tyr ABCA4 p.Gly991Arg ABCA4 p.Gly172Ser ABCA4 p.Arg152Gln ABCA4 p.Ile1846Thr ABCA4 p.Arg943Gln ABCA4 p.His423Arg ABCA4 p.Glu471Lys ABCA4 p.Arg219Thr ABCA4 p.Gly65Glu ABCA4 p.Glu1399Lys ABCA4 p.Asp645Asn ABCA4 p.Pro143Leu ABCA4 p.Leu2035Pro ABCA4 p.Ile824Thr ABCA4 p.Trp697* ABCA4 p.Ser336Cys Mutations Detected in theTwoTest Populations by the ABCR400 Array,That Had Not Been Found by SSCP Number Nucleotide change Protein e¡ect Number of cases 1 161G4A C54Y 3 2 194G4A G65E 1 3 428C4T P143L 1 4 455G4A R152Q 1 5 514G4A G172S 1 6 635G4A R212H 1 7 656G4C R219T 1 8 768G4Ta Splice/V256V 3 9 1007C4G S336C 2 10 1268A4G H423R 4 11 1411G4A E471K 2 12 1622T4Ca L541P 8 13 1933G4A D645N 1 14 2041C4T R681X 5 15 2090G4A W697X 1 16 2471T4C I824T 1 17 2588G4Ca Splice/G863A 5 18 2828G4A R943Q 1 19 2966T4C V989A 1 20 2971G4C G991R 1 21 4139C4T P1380L 8 22 4195G4A E1399K 1 23 4328G4A R1443H 1 24 4457C4T P1486L 1 25 4462T4Ca C1488R 1 26 4469G4Aa C1490Y 1 27 4918C4Ta R1640W 2 28 IVS40+5G4A Splice 2 29 5537T4C I1846T 2 30 5882G4A G1961E 5 31 6089G4A R2030Q 1 32 6104T4C L2035P 1 33 6449G4A C2150Y 1 Mutation numbering is based on the cDNA sequence (GenBank NM_000350). Login to comment 127 ABCA4 p.Gly1961Glu The most frequent individual allele in all cohorts was, with one exception, the 5882G>A (G1961E) mutation, ranging from 7% in the NEI/NIH cohort to >21% in the Slovenian sample (Table 3). Login to comment 129 ABCA4 p.Gly863Ala Of the other frequent variants, the 2588G>C (G863A/delG863) allele was frequent in the U.S. and Dutch cohorts, while completely absent in populations from South Europe, Italy, and Slovenia. Login to comment 130 ABCA4 p.Leu541Pro A similar trend was observed for the IVS38-10T>C and 1622T>C; 3113C>T (L541P;A1038V) alleles. Login to comment 132 ABCA4 p.Arg681* ABCA4 p.Gln1412* The same was true for two nonsense mutations, 2041C>T (R681X) and 4234C>T (Q1412X), which were detected at >7% each in the Slovenian STGD sample but not in other populations. Login to comment 155 ABCA4 p.Gly863Ala ABCA4 p.Leu541Pro These calculations also assume that all ''major`` alleles have been found in European populations, for example 2588G>C (G863A/delG863) in the Dutch and 1622T>C; 3113C>T (L541P;A1038V) in Germans. Login to comment 193 ABCA4 p.Cys1502* A heterozygous 4506C>A (C1502X) nonsense change was detected in one STGD subject from Columbia University. Login to comment 194 ABCA4 p.Gly991* In the Italian cohort we detected two new variants, one of which was a homozygous 2971G>T (G991X) nonsense mutation in one STGD patient. Login to comment 195 ABCA4 p.Gly991Arg The previously known sequence change at that position was 2971G>C (G991R). Login to comment