ABCMdb

PMID: 23096905

Oldani M, Marchi S, Giani A, Cecchin S, Rigoni E, Persi A, Podavini D, Guerrini A, Nervegna A, Staurenghi G, Bertelli M
Clinical and molecular genetic study of 12 Italian families with autosomal recessive Stargardt disease.
Genet Mol Res. 2012 Dec 17;11(4):4342-50. doi: 10.4238/2012.October.9.3., [PubMed]

Sentences

No. Mutations Sentence Comment

7 ABCA4 p.Gly1961Glu The most frequent mutation was G1961E, found in 17% of families (2/12). Login to comment 9 ABCA4 p.Tyr1858Asp ABCA4 p.Tyr850Cys ABCA4 p.Thr959Ala Four new mutations were also identified: Tyr1858Asp, Leu1195fsX1196, p.Tyr850Cys, and p.Thr959Ala. Login to comment 27 ABCA4 p.Cys2150Tyr Although preliminary and fragmented, these studies have established that mutations in the active site of the nucleotide-binding domain 2 of the protein (for example, the mutation C2150Y) are the most severe, followed by large deletions leading to truncated proteins. Login to comment 35 ABCA4 p.Gly1961Glu The most interesting aspect is that mutation G1961E is the most common in Italy and is associated with a milder phenotype (Simonelli et al., 2005; Passerini et al., 2010; Sodi et al., 2010). Login to comment 69 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly863Ala ABCA4 p.Arg18Trp ABCA4 p.Cys1488Arg ABCA4 p.Arg1098Cys ABCA4 p.Val767Asp ABCA4 p.Arg2030Gln ABCA4 p.Arg2030Gln ABCA4 p.Cys2150Tyr ABCA4 p.Ile156Val ABCA4 p.Asp1532Asn ABCA4 p.Met1Val ABCA4 p.Met1Val ABCA4 p.Gly607Arg ABCA4 p.Tyr1858Asp ABCA4 p.Tyr850Cys ABCA4 p.Thr959Ala of patients Subject Allele 1 Allele 2 Age of diagnosis (years) Visual acuity Right eye Left eye 1 F1 ID81 Tyr1858Asp Met1Val; Arg2030Gln 22 20/50 20/32 2 F2 ID220 Ile156Val Gly607Arg; Gly1961Glu 30 20/800 20/400 3 F3 ID362 Met1Val Gly1961Glu; Arg2030Gln 60 20/40 20/32 4 F4 ID197 Asp1532Asn Arg2030term 40 20/32 20/32 5 F6 ID363 Tyr362Term Gly863Ala 16 20/200 20/250 6 F7 ID365 Arg1098Cys Cys1488Arg 50 20/32 20/800 7 F8 ID394 Arg18Trp Val767Asp 10 20/800 20/800 8 F9 ID396 IVS40+5G>A IVS13+1G>A 19 20/40 20/50 9 F10 ID366 p.Gln1513Profs*42 - 20 20/200 20/200 10 F12 ID377 Leu1195Argfs*2 - 50 20/32 20/20 11 F13 ID4 Cys2150Tyr - 70 20/400 20/400 12 F17 ID457 p.Tyr850Cys p.Thr959Ala 50 20/20 20/40 F1 = family 1; ID = reference code to a specific patient. Login to comment 72 ABCA4 p.Tyr1858Asp In family F1 we found the new mutation Tyr1858Asp, in which an amino acid with an aromatic ring with high stearic hindrance was substituted for another having an alcohol group but only small variations in polarity (from acid polarity to neutral). Login to comment 77 ABCA4 p.Leu1195Arg This insertion leads to a reading frame shift in the coding region downstream, which results in a change in amino acid 1195 from leucine to arginine and the appearance of a stop codon in the next position, generating a truncated protein. Login to comment 78 ABCA4 p.Tyr850Cys ABCA4 p.Thr959Ala In family F17 we found two 2 new mutations, p.Tyr850Cys and p.Thr959Ala. Login to comment 90 ABCA4 p.Gly1961Glu In patients with the G1961E mutation, the most frequent ABCA4 alleles in Italian STGD patients, we observed various clinical features: one patient had late onset of the disease (30 years) and showed multiple foci of hypoautofluorescence surrounded by a hyperautofluorescent area in the macular region. Login to comment 95 ABCA4 p.Gly1961Glu For example, patients with the G1961E mutation had extremely different ages of onset and fundus findings. Login to comment 107 ABCA4 p.Gly1961Glu The most frequent mutation was G1961E, found in 17% of families. Login to comment