ABCMdb

ABCA4 p.Cys2137Tyr

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Publications

PMID: 19959634 [PubMed] Aguirre-Lamban J et al: "Comparison of high-resolution melting analysis with denaturing high-performance liquid chromatography for mutation scanning in the ABCA4 gene."

No. Sentence Comment

12 One homozygous mutation was not detected by dHPLC; however, the p.Cys2137Tyr homozygote was distinguished from the wild-type by HRM technique. In the same way, one novel change in exon 5 (p.Arg187His) was found only by means of the HRM technique. In addition, dHPLC identified the mutation p.Trp1724Cys in one sample; however, HRM detected the mutation in two samples. Login to comment
66 Homozygous sequence alteration (p.Cys2137Tyr) could be identified from wild-type by HRM analyses (Fig. 1). Login to comment
90 Normalized and Temp-Shifted Difference Plot T empera ture (°C) 89.5 89 88.5 88 87.5 87 86.5 86 85.5 85 84.5 R elative S ignal Difference 16.539 15.039 13.539 12.039 10.539 9.039 7.539 6.039 4.539 3.039 1.539 0.039 -1.461 A B p.Cys2137Tyr het p.Cys2137Tyr hom WT p.Cys2137Tyr het p.Cys2137Tyr hom WT FIGURE 1. Login to comment
92 (A) Melting curves for two wild-type (WT), one p.Cys2137Tyr heterozygous (het), and one p.Cys2137Tyr homozygous (hom) sample. Login to comment
93 (B) dHPLC profile of the heterozygous (het) p.Cys2137Tyr, the homozygous (hom) p.Cys2137Tyr, and the WT control sample. Login to comment
111 In contrast, dHPLC depends on a specific temperature that requires optimization.19 It generally is accepted that routine dHPLC scanning does not detect homozygous sequence alterations, but the situation for melting analyses is less clear.20 In this study, a homozygous mutation (p.Cys2137Tyr) was detected by HRM. Login to comment
63 Homozygous sequence alteration (p.Cys2137Tyr) could be identified from wild-type by HRM analyses (Fig. 1). Login to comment
97 In contrast, dHPLC depends on a specific temperature that requires optimization.19 It generally is accepted that routine dHPLC scanning does not detect homozygous sequence alterations, but the situation for melting analyses is less clear.20 In this study, a homozygous mutation (p.Cys2137Tyr) was detected by HRM. Login to comment

PMID: 19028736 [PubMed] Aguirre-Lamban J et al: "Molecular analysis of the ABCA4 gene for reliable detection of allelic variations in Spanish patients: identification of 21 novel variants."

No. Sentence Comment

42 Three missense changes were detected (p.Ala762Glu, p.Ile2047Asn and p.Cys2137Tyr) in patients but not in the 100 ethnically matched control chromosomes. Login to comment
80 Clinical science Br J Ophthalmol 2009;93:614-621. doi:10.1136/bjo.2008.145193 Table 1 Clinical findings of the Spanish patients with Stargardt disease (STGD), autosomal recessive cone-rod dystrophy and autosomal recessive retinitis pigmentosa Pedigree Age (years) Age (years) of onset Visual acuity Diagnosis Allele 1 Allele 2 Segregation OD OS Nucleotide changes (exons) Amino acid change Nucleotide changes (exons) Amino acid change ARDM-135 42 24 0.4 0.6 STGD c.5882G.A(42) p.Gly1961Glu c.1029_1030insT(8) p.Asn344fsX NP ARDM-240 15 13 0.2 0.16 STGD c.5882G.A(42) p.Gly1961Glu c.2285C.A(15) p.Ala762Glu Yes ARDM-225 32 25 0.25 0.50 STGD c.5882G.A(42) p.Gly1961Glu c.6559C.T(48) p.Gln2187X Yes ARDM-164 21 11 NA STGD c.3386G.T(23) p.Arg1129Leu c.700C.T(6) p.Gln234X Yes ARDM-162 50 16 0.1 0.1 STGD c.3386G.T(23) p.Arg1129Leu ND ND Yes ARDM-198 27 19 0.1 0.1 STGD c.3386G.T(23) p.Arg1129Leu ND ND NP ARDM-125 31 9 0.3 0.4 STGD c.3211insGT(22) FS p.KNLFA1876dup Yes ARDM-158 24 9 0.2 0.2 STGD c.3211insGT(22) FS c.4537delC(30) p.Gln1513fsX1525 NP ARDM-165 40 30 NA STGD c.3211insGT(22) FS ND ND NP ARDM-167 49 23 0.05 0.05 STGD c.3211insGT(22) FS ND ND NP ARDM-146 32 13 0.06 0.1 STGD c.3056C.T(21) p.Thr1019Met c.6140T.A(44) p.Ile2047Asn Yes ARDM-40 46 9 0.1 0.1 STGD c.3056C.T(21) p.Thr1019Met c.3943C.T(27) p.Gln1315X Yes ARDM-90 26 8 Hand moving STGD c.5929G.A (43) p.Gly1977Ser IVS21-2A.T Yes ARDM-181 57 16 0.1 0.09 STGD c.3323G.A (22) p.Arg1108His IVS38+5G.A Yes ARDM-197 35 15 0.1 0.1 STGD c.4793C.A(34) (false +) p.Ala1598Asp (false +) c.5172G.T(36) p.Trp1724Cys Yes ARDM-183 63 55 0.150 0.175 STGD c.6079C.T(44) p.Leu2027Phe c.5929G.A(43) (false -) p.Gly1977Ser (false -) NP ARDM-38 35 6 0.01 0.02 STGD c.1804C.T(13) p.Arg602Trp c.4739delT(33) p.Leu1580fs Yes ARDM-163 48 32 0.01 0.32 STGD c.4457C.T(30) p.Pro1486Leu ND ND Yes ARDM-166 42 39 NA STGD c.6320G.A(46) p.Arg2107His ND ND Yes ARDM-222 26 23 NA STGD c.2791G.A(19) p.Val931Met ND ND NP ARDM-160 30 5 0.25 0.1 STGD ND ND ND ND Yes ARDM-173 49 7 NA STGD ND ND ND ND Yes ARDM-205 NA NA NA STGD c.4919G.A(35) p.Arg1640Gln ND ND NP ARDM-247 30 12 0.05 0.1 CRD c.3386G.T(23) p.Arg1129Leu c.6410G.A(47) p.Cys2137Tyr Yes ARDM-99 59 46 0.05 0.05 CRD c.4297G.A(29) p.Val1433Ile ND ND NP ARDM-131 27 15 0.9 0.7 CRD c.2701A.G(18) p.Thr901Ala ND ND Yes ARDM-100 28 4 0.2 0.16 CRD ND ND ND ND Yes ARDM-142 30 25 0.8 0.5 CRD ND ND ND ND Yes RP-773 38 20 0.05 0.05 RP c.33N86G.T(23) p.Arg1129Leu ND ND NP RP-959 53 10 0.1 0.1 RP c.466A.G(5) p.Ile156Val ND ND Yes RP-1058 37 6 0.2 0.6 RP c.4297G.A(29) p.Val1433Ile ND ND NP Twenty-seven out of 31 subjects were found to be compound heterozygous for mutations in the ABCA4 gene detected by microarray. Login to comment
100 In previous studies of the Spanish population, the p.Arg1129Leu variant was identified as a major mutant allele which accounted for 24% of the STGD alleles.14 This variant has been postulated to have a moderately severe effect and has predominantly been associated with a STGD phenotype.14 In contrast, the prevalence of this mutation in patients from North America was less than 1%.15 Interestingly, we identified one 30-year-old patient (ARDM-247), double heterozygous for the p.Arg1129Leu and p.Cys2137Tyr alleles, who presented a CRD phenotype. Login to comment
101 This p.Cys2137Tyr change was located more towards the amino terminus. Login to comment
102 Moreover, in other study, the results showed that the changes located in this zone appear to result in altered processing of the protein and to be associated with an earlier onset of disease.16 The p.Cys2137Tyr change in combination with the p.Arg1129Leu allele produced a CRD phenotype. Login to comment
103 Therefore, we speculate that the novel p.Cys2137Tyr variant could be a severe allele which is modifying the patient`s phenotype. Login to comment