ABCMdb

ABCA4 p.Glu1122Asp

ClinVar:	c.3366G>C , p.Glu1122Asp ? , not provided c.3364G>A , p.Glu1122Lys D , Pathogenic
Predicted by SNAP2:	A: N (57%), C: N (57%), D: D (91%), F: N (53%), G: N (57%), H: N (57%), I: N (57%), K: D (95%), L: N (53%), M: N (53%), N: N (66%), P: N (57%), Q: N (61%), R: N (53%), S: N (61%), T: N (66%), V: N (61%), W: D (71%), Y: N (53%),
Predicted by PROVEAN:	A: D, C: D, D: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D,

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Publications
[hide] ABCA4 gene mutations in Japanese patients with Sta... Invest Ophthalmol Vis Sci. 2002 Sep;43(9):2819-24. Fukui T, Yamamoto S, Nakano K, Tsujikawa M, Morimura H, Nishida K, Ohguro N, Fujikado T, Irifune M, Kuniyoshi K, Okada AA, Hirakata A, Miyake Y, Tano Y
ABCA4 gene mutations in Japanese patients with Stargardt disease and retinitis pigmentosa.
Invest Ophthalmol Vis Sci. 2002 Sep;43(9):2819-24., [PMID:12202497]

Abstract [show]
PURPOSE: To evaluate photoreceptor cell-specific adenosine triphosphate (ATP)-binding cassette transporter (ABCA4) gene mutations in Japanese patients with Stargardt disease (STGD) and the correlation of these mutations to clinical phenotypes. METHODS: Serum was obtained from 10 unrelated Japanese patients with STGD and 96 unrelated Japanese patients with autosomal recessive retinitis pigmentosa (arRP). All 50 ABCA4 gene exons of the patients with STGD were screened for mutations by a combination of single-strand conformation polymorphism analysis and polymerase chain reaction (PCR) direct-sequencing techniques. By restriction enzyme digestion, primer extension analysis, and PCR direct sequencing techniques, the patients with arRP were screened for three segregated, presumably null ABCA4 gene mutations observed in Japanese patients with STGD. RESULTS: Three novel, presumably null mutations of the ABCA4 gene, IVS7-45_952delinsTCTGACC, IVS12+2T-->G, and 1894delA, were identified. The Arg2149stop mutation that had been found in a white patient with STGD in a prior study was also found in a Japanese patient. Two arRP-affected siblings and two unrelated patients with STGD were found to be homozygous for the same IVS12+2T-->G mutation, and three other arRP-affected siblings were carriers of the IVS12+2T-->G mutation and/or the IVS7-45_952delinsTCTGACC mutation. These three siblings with arRP showed only atrophic degeneration in the macula early after the onset of the disease, and STGD had been diagnosed. CONCLUSIONS: Three novel ABCA4 gene mutations were identified in Japanese patients with STGD and arRP. Mutations in the ABCA4 gene can cause panretinal degeneration that changes its clinical appearance from STGD to arRP over time.

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No. Sentence Comment
36 Screening of 96 normal control subjects for 17 sequence variations, cosegregation analyses of two STGD-affected families and two arRP-affected families, and screening of 96 Japanese patients with arRP for three segregated, presumably null mutations observed in Japanese patients with STGD were performed by restriction digestion, primer extension analysis, and direct sequencing.21 Because the IVS7-45_952delinsTCTGACC mutation causes a 139-bp deletion, the PCR products were analyzed by electrophoresis on a 2% agarose gel. The IVS12ϩ2T3G mutation creates a FokI (TaKaRa, Tokyo, Japan) recognition site (5Ј-GGATG(N)9-3Ј); the Ile604Ser mutation a PvuII (TaKaRa) recognition site (5Ј-CAGCTG-3Ј); the 1894delA mutation a XhoII (TaKaRa) recognition site (5Ј-RGATCY-3Ј); the Glu1122Asp mutation a Hin1I (TaKaRa) recognition site (5Ј-GRCGYC-3Ј); and the Leu1583Pro mutation an EcoRII (TaKaRa) recognition site (5Ј-CCWGG-3Ј). Login to comment
39 The IVS7-45_952delinsTCTGACC, IVS12ϩ2T3G, IVS12-50G3A, Ile604Ser, 1894delA, Glu1122Asp, Leu1583Pro, Gly1623Ser, IVS38-36delT, Met1882Val, Arg2149stop, and Phe2188Ser sequence variations were not found in the 192 normal control alleles. Login to comment
46 ABCA4 Gene Sequence Variations Nucleotide change Effect STGD (20†) Control (192†) Reference IVS7-45_952delinsTCTGACC* Splice 0 0 This study IVS12ϩ2T3G* Splice 5 0 This study IVS12-50G3A Unkown 1 0 23 T1811G Ile604Ser 1 0 This study 1894delA Frameshift 1 0 This study G3366C Glu1122Asp 1 0 This study T4748C Leu1583Pro 1 0 This study G4867A Gly1623Ser 1 0 This study IVS38-36delT Unkown 1 0 This study A5644G Met1882Val 2 0 This study G5682C Leu1894Leu 4 32 12,13,14,16,22,23 A5814G Leu1938Leu 4 32 12,14,23 IVS41-11G3A Unkown 4 32 11,14,16,23 A5844G Pro1948Pro 4 32 11,12,14,16,22,23,24,27 T6285C Asp2095Asp 3 27 11,12,14,16,23 C6445T Arg2149Stop 1 0 15 T6563C Phe2188Ser 1 0 This study * Mutations observed in patients with arRP. Login to comment
61 The IVS7-45_952delinsTCTGACC, IVS12ϩ2T3G, Ile604Ser, 1894delA Glu1122Asp, Leu1583Pro, Gly1623Ser, Met1882Val, Arg2149stop, and Phe2188Ser sequence variations were not found in the 192 normal control alleles tested, and hence these FIGURE 2. Login to comment
59 The IVS7-45_952delinsTCTGACC, IVS12af9;2T3G, Ile604Ser, 1894delA Glu1122Asp, Leu1583Pro, Gly1623Ser, Met1882Val, Arg2149stop, and Phe2188Ser sequence variations were not found in the 192 normal control alleles tested, and hence these FIGURE 2. Login to comment