ABCMdb

PMID: 10958761

Maugeri A, Klevering BJ, Rohrschneider K, Blankenagel A, Brunner HG, Deutman AF, Hoyng CB, Cremers FP
Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy.
Am J Hum Genet. 2000 Oct;67(4):960-6. Epub 2000 Aug 24., [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCA4 p.Leu541Pro One complex ABCA4 allele (L541P;A1038V) was found exclusively in German patients with CRD; one patient carried this complex allele homozygously, and five others were compound heterozygous. Login to comment 32 ABCA4 p.Gly1961Glu ABCA4 p.Asp2177Asn ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Leu541Pro ABCA4 p.Ala1598Asp ABCA4 p.Gln2220* ABCA4 p.Trp2110* Although the significance of this finding is under debate (Stone et al. 1998), at least two ABCA4 mutations (G1961E and D2177N) have been shown, in a large multicenter study, to be statistically more frequent in patients Table 1 ABCA4 Mutations in Patients with CRD PATIENT INHERITANCE ABCA4 ALLELE 1 ABCA4 ALLELE 2 Nucleotide Changes Effects Nucleotide Changes Effects 9250a Isolated 1622TrC;3113CrT L541P;A1038Vb 194GrA G65Eb 9303 AR 1622TrC;3113CrT L541P;A1038Vb 9336 Isolated 6658CrT Q2220X 9369a AR 6601-6602delAG Frameshift 9370 Isolated 1622TrC;3113CrT L541P;A1038Vb 9371 Isolated 1622TrC;3113CrT L541P;A1038Vb 1622TrC;3113CrT L541P;A1038Vb 9378a Isolated 768GrT 5 Splice mutationb 9553 AR 2588GrC DG863/G863Ab IVS35del-2rϩ2del4 3 Splice mutation 9633 Isolated 1622TrC;3113CrT L541P;A1038Vb 4469GrA C1490Yb 9650 Isolated 3364GrA E1122Kb 9887 Isolated 4793CrA A1598D 6329GrA W2110X 11872 Isolated 634CrT R212Cb 13163a AR 1622TrC;3113CrT L541P;A1038Vb IVS36ϩ1GrA 5 Splice mutationb a Patient with atypical CRD. Login to comment 60 ABCA4 p.Leu541Pro In another patient (8547), there was only Figure 2 DNA sequences in patients carrying the complex ABCA4 allele L541P;A1038V. Login to comment 75 ABCA4 p.Ala1598Asp One is a missense mutation (A1598D) that was not found in 100 control individuals. Login to comment 76 ABCA4 p.Gln2220* ABCA4 p.Trp2110* Four are thought to represent null mutations, either because they introduce a stop codon (W2110X and Q2220X), result in a frameshift (6601-6602delAG), or disrupt a splice site (IVS35- 2rϩ2del4). Login to comment 77 ABCA4 p.Leu541Pro A complex L541P;A1038V allele was found in 7 of 19 mutant alleles. Login to comment 105 ABCA4 p.Leu541Pro Seven alleles in six German patients with CRD were found to carry two missense mutations (L541P;A1038V). Login to comment 107 ABCA4 p.Ala1038Val The ABCA4 allele carrying only the A1038V mutation is one of the most frequent alleles in patients with STGD1 in the United States (15/150) (Lewis et al. 1999). Login to comment 108 ABCA4 p.Leu541Pro However, among a total of 357 non-German patients with STGD1, only 4 (1.1%) were shown to carry the L541P;A1038V allele (Rozet et al. 1998; Fishman et al. 1999; Lewis et al. 1999; Maugeri et al. 1999; Papaioannou et al. 2000; Simonelli et al. 2000). Login to comment