ABCMdb

PMID: 10442900

De La Paz MA, Guy VK, Abou-Donia S, Heinis R, Bracken B, Vance JM, Gilbert JR, Gass JD, Haines JL, Pericak-Vance MA
Analysis of the Stargardt disease gene (ABCR) in age-related macular degeneration.
Ophthalmology. 1999 Aug;106(8):1531-6., [PubMed]

Sentences

No. Mutations Sentence Comment

80 ABCA4 p.Asp2177Asn The only variant we found in our study population was D2177N, Asp2177 3 Asn2177 .31 We identified this change in two of our sporadic AMD patients (3.8%) and in none of the familial or population cases. Login to comment 85 ABCA4 p.Gly863Ala ABCA4 p.Ser2255Ile In addition to screening for the previously reported variants, we screened our population for the five most common ABCR polymorphisms reported by Allikmets et al31 (U843G, D8464H, G863A, R934Z, S2255I) and failed to identify any of these particular polymorphisms in our study. Login to comment 89 ABCA4 p.Pro862Leu One variant (P862L) was identified in only seven affected individuals. Login to comment 93 ABCA4 p.Ala1038Val A second variant was identified (A1038V) in an unaffected member of an AMD family and in no other individuals. Login to comment 95 ABCA4 p.Asn1868Ile One polymorphism (N1868I) occurred in both the randomly selected population group and affected subjects and failed to segregate with the disease phenotype in the families. Login to comment 97 ABCA4 p.Thr901Ala A second polymorphism, T901A, was identified in five affected patients within two AMD families (Fig 2) and in one member of the randomly selected population. Login to comment 99 ABCA4 p.Thr901Ala The other familial T901A variant appeared in one affected member of a family of two affected cousins (one with grade 5 AMD demonstrated the variant; another with grade 3 AMD did not). Login to comment 107 ABCA4 p.Gly1961Glu ABCA4 p.Asp2177Asn ABCA4 p.Leu1970Phe ABCA4 p.Ile1562Thr ABCA4 p.Arg1898His ABCA4 p.Arg1129Leu ABCA4 p.Glu471Lys ABCA4 p.Thr1428Met ABCA4 p.Arg1517Ser ABCA4 p.Gly1578Arg Number of Age-related Macular Degeneration (AMD) Cases with Variants* Mutation Duke (n ‫؍‬ 169)† D2177N 2 (1.2%) E471K 0 R1129L 0 T1428M 0 R1517S 0 I1562T 0 G1578R 0 5169 ϩ 1G 3 A 0 R1898H 0 G1961E 0 L1970F 0 6519⌬11bp 0 6568⌬C 0 Total 2 (1.2%) * Variants considered to be associated with the genetic etiology of AMD by Allikmets et al.31 † Independent cases are determined by counting 1 familial AMD case from each of the 112 families and adding the 57 sporadic AMD cases, for a total of 169 cases. Login to comment 111 ABCA4 p.Asp2177Asn In the report by Allikmets et al, the D2177N variant was one of the most common variants identified (7 [4.2%] of 167 individual AMD cases) and accounted for 27% of the ABCR variants among their AMD study population. Login to comment 112 ABCA4 p.Asp2177Asn One D2177N variant was identified among the 220 controls that they studied. Login to comment 116 ABCA4 p.Thr901Ala One of these, T901A, is of greatest interest because it was found among all the affected members of one of our larger AMD families. Login to comment 120 ABCA4 p.Pro862Leu Pedigree showing variant P862L. Login to comment 124 ABCA4 p.Thr901Ala Pedigrees showing polymorphism T901A. Login to comment 131 ABCA4 p.Asn1868Ile ABCA4 p.Thr901Ala ABCA4 p.Pro862Leu of Controls (%) P862L 2682 C 3 T 2683 C 3 T 3/112 (3.6) 3/53 (3.8) 0/56 (0) T901A 2782 A 3 G 2/112 (1.8) 0/53 (0) 1/56 (1.8) N1868I 5684 A 3 T 3/112 (2.7) 4/53 (7.5) 4/56 (7.1) L1948P* 5924 T 3 C 112/112 (100) 53/53 (100) 56/56 (100) L1948P* 5924 T 3 C 5925 G 3 A 110/112 (98) 51/53 (96) 54/56 (96) I2023I 6150 C 3 T 9/112 (8) 5/53 (9.4) 3/56 (5.4) L2026L 6160 C 3 T 0/112 (0) 0/53 (0) 0/56 (0) I2083I 6330 C 3 T 9/112 (8) 4/53 (7.5) 5/56 (8.9) * Variants identified in probands only. Login to comment 134 ABCA4 p.Asp2177Asn With the exception of the D2177N variant in two AMD sporadic individuals, our collective findings differ significantly from those of Allikmets et al.31 Our observed rate of ABCR variants (1.2%) is significantly lower than their 16% (P Ͻ 0.00001). Login to comment