ABCMdb

PMID: 10634594

Papaioannou M, Ocaka L, Bessant D, Lois N, Bird A, Payne A, Bhattacharya S
An analysis of ABCR mutations in British patients with recessive retinal dystrophies.
Invest Ophthalmol Vis Sci. 2000 Jan;41(1):16-9., [PubMed]

Sentences

No. Mutations Sentence Comment

43 ABCA4 p.Gly863Ala ABCA4 p.Cys54Tyr ABCA4 p.Arg943Gln In the family of a STGD/FFM patient, three sequence alterations Cys-54-Tyr, Gly-863-Ala, and Arg-943-Gln in ABCR exons 3, 17, and 19, respectively, were found to be present. Login to comment 44 ABCA4 p.Gly863Ala ABCA4 p.Arg943Gln Both the Gly-863-Ala and Arg-943-Gln substitutions were present in the unaffected mother who had no clinical evidence of the disease at the age of 58 years. Login to comment 45 ABCA4 p.Gly863Ala ABCA4 p.Arg1640Trp ABCA4 p.Cys54Tyr ABCA4 p.Arg602Trp ABCA4 p.Asn96His ABCA4 p.Asn96Asp ABCA4 p.Cys2150Tyr ABCA4 p.Ile156Val ABCA4 p.Ser445Arg ABCA4 p.Ala407Val ABCA4 p.Val1429Ala ABCA4 p.Lys2160Arg ABCA4 p.Val424Ala ABCA4 p.Gln1703Lys Neither of these putative TABLE 1. List of Mutations Found in 70 Patients of British Origin Nucleotide Change Amino Acid Change No. of Patients (/70) Phenotype No. of Controls (/96) G161A Cys-54-Tyr 1 STG/FFM NF A286G Asn-96-Asp 1 STG/FFM NF A286C Asn-96-His 1 STG/FFM NF A466G Ile-156-Val 1 STG/FFM NF C1220T Ala-407-Val 6 STG/FFM, arCRD NF T1271C Val-424-Ala 2 STG/FFM, arRP NF C1335G Ser-445-Arg 1 STG/FFM NF C1804T Arg-602-Trp 1 STG/FFM NF C2337A Cys-779-Ter 1 STG/FFM NF *G2588C Gly-863-Ala 5 STG/FFM 2/176 3392delC 1147 Ter 1 STG/FFM NF T4286C Val-1429-Ala 1 STG/FFM NF 4774-2A3C Splice acceptor 2 STG/FFM NF †C4918T Arg-1640-Trp 1 STG/FFM NF C5107G Gln-1703-Lys 1 STG/FFM NF 5161delAC Frameshift 1 STG/FFM NF C5337G Tyr-1779-Ter 1 STG/FFM NF C6088T Arg-2030-Ter 1 arCRD NF 6282ϩ7G3A Splice donor 1 STG/FFM NF G6449A Cys-2150-Tyr 2 arCRD NF A6479G Lys-2160-Arg 1 STG/FFM NF * Independently reported by Allikmets et al.6 † Independently reported by Rozet et al.8 NF, not found in 96 ethnically matched control individuals. Login to comment 46 ABCA4 p.Pro1948Leu ABCA4 p.Arg943Gln TABLE 2. List of Polymorphisms Found in 70 Patients of British Origin Nucleotide Change Exon Amino Acid Change No. of Patients (/70) No. of Controls (/96) 1356ϩ11delG 10 intron - 2 NF *G2828A 19 Arg-943-Gln 8 16/176 3815-82G3C 25 intron - 1 NF G5682C 40 Leu-1894-Leu 1 30 C5842T 42 Pro-1948-Leu 4 7 G5844A 42 Pro-1948-Pro 12 22 T5885C 42 Val-1962-Val 9 NF 6006-16G3A 43 intron - 19 NF 6729ϩ21C3T 48 intron - 2 NF 6816ϩ27G3C 49 intron - 4 NF * Independently reported by Allikmets et al.6 NF, not found. Login to comment 47 ABCA4 p.Cys54Tyr mutations was detected in the unaffected father, in whom the third alteration (Cys-54-Tyr) was identified. Login to comment 49 ABCA4 p.Gly863Ala ABCA4 p.Arg943Gln We therefore assumed that the two sequence changes Gly-863-Ala and Arg-943-Gln were in-cis on the maternally inherited chromosome, comprising a "complex" allele. Login to comment 51 ABCA4 p.Gly863Ala ABCA4 p.Arg943Gln When screening additional patients, we discovered that four more individuals affected with STGD/FFM carried the same two changes in-cis (Gly-863-Ala and Arg-943-Gln). Login to comment 53 ABCA4 p.Asn96His ABCA4 p.Ala407Val ABCA4 p.Val424Ala In addition, three of these affected individuals also carried a third sequence variation (Asn-96-His, Ala-407-Val, or Val-424-Ala) derived from the other parental chromosome. Login to comment 62 ABCA4 p.Gly863Ala ABCA4 p.Arg943Gln The allele in question is the "complex" one carrying two sequence changes, Gly-863-Ala and Arg-943-Gln, in-cis. Login to comment 65 ABCA4 p.Gly863Ala ABCA4 p.Arg943Gln Of the two amino acid alterations in-cis, Gly-863-Ala besides being a putative missense mutation could also affect proper RNA splicing as it occurs at the acceptor splice site of exon 17.13 The second alteration, Arg-943-Gln, has been classified as a "polymorphism. Login to comment 69 ABCA4 p.Gly863Ala ABCA4 p.Arg943Gln Ancestral Haplotype Shared by the 5 Families Carrying the Two Amino Acid Alterations Gly-863-Ala and Arg-943-Gln in-cis Marker Distance Family 1 Family 2 Family 3 Family 4 Family 5 1a 1b 1c 1d 2a 2b 5a 5b D1S198 2 2 2 2 2 2 2 2 2 2 6.2 D1S216 2 2 2 2 2 2 2 2 2 2 10.4 D1S207 3 3 3 3 3 3 - 3 3 3 11.9 D1S2813 1 1 1 1 1 1 1 1 1 1 ABCR gene 2.9 D1S236 1 1 1 1 1 1 1 1 1 1 10.9 D1S248 4 4 4 4 5 5 5 5 2 2 11.8 D1S252 1 1 1 1 1 1 - 1 2 2 9.0 D1S305 1 1 1 1 1 1 2 - 2 2 Column 1 denotes the markers used for haplotyping analysis, and column 2 shows the genetic distance between the respective markers (in cM). Login to comment