ABCMdb

PMID: 10711710

Simonelli F, Testa F, de Crecchio G, Rinaldi E, Hutchinson A, Atkinson A, Dean M, D'Urso M, Allikmets R
New ABCR mutations and clinical phenotype in Italian patients with Stargardt disease.
Invest Ophthalmol Vis Sci. 2000 Mar;41(3):892-7., [PubMed]

Sentences

No. Mutations Sentence Comment

55 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Ala1038Val ABCA4 p.Arg212Cys ABCA4 p.Arg212Cys ABCA4 p.Arg212Cys ABCA4 p.Arg212Cys ABCA4 p.Arg212Cys ABCA4 p.Arg212Cys ABCA4 p.Arg1640Gln ABCA4 p.Arg1640Gln ABCA4 p.Arg1640Gln ABCA4 p.Arg1640Gln ABCA4 p.Arg1640Gln ABCA4 p.Arg1640Gln ABCA4 p.Val767Asp ABCA4 p.Val767Asp ABCA4 p.Glu1087Lys ABCA4 p.Glu1087Lys ABCA4 p.Thr897Ile ABCA4 p.Thr897Ile ABCA4 p.Thr897Ile ABCA4 p.Thr897Ile ABCA4 p.Glu1399Lys ABCA4 p.Glu1399Lys Clinical Characteristics and Segregation of Mutations in 11 Italian STGD/FFM Pedigrees Pedigree Patients Age Age of Onset Visual Acuity Diagnosis Allele 1 Allele 2 431 431 S 18 10 20/200 STGD R212C R212C 433 D 29 8 20/200 STGD R212C R212C 432 F 63 10 LE 20/40RE LP High myopia with macular involvement R212C R212H(p) 858 Gm 87 10 LP High myopia with macular involvement wt R212H(p) 774 M 60 58 20/25 Pigmentary abnormalities and drusen R212C wt 260 D 41 35 20/200 STGD 250ƒCAAA G1961E 759 S 39 38 20/100 STGD 250ƒCAAA G1961E 760 M 60 57 20/40 Pigmentary abnormalities and drusen wt G1961E 761 Gs 20/20 Normal wt G1961E 762 Gs 20/20 Normal 250ƒCAAA wt 631 631 S 18 3 20/200 STGD / FFM 5018 ϩ 2T 3 C 5018 ϩ 2T 3 C 777 F 59 58 20/20 Soft distinct drusen 5018 ϩ 2T 3 C wt 779 M 52 50 20/20 Hard distinct drusen 5018 ϩ 2T 3 C wt 624 624 D 40 18 20/200 STGD R1640Q G1961E 625 S 36 20 20/200 STGD R1640Q G1961E 834 M 74 20/20 Normal R1640Q wt 636 636 S 22 15 20/400 STGD / FFM E1087K G1961E 778 M 43 43 20/20 Hard distinct drusen wt G1961E 632 632 D 24 8 20/200 STGD / FFM 250ƒCAAA V767D 628 628 S 27 18 20/200 STGD T897I N/D 4 F 63 20/20 Normal wt N/D 5 M 62 62 20/20 Pigmentary abnormalities and drusen T897I N/D 633 633 D 12 8 20/400 STGD / FFM A1038V N/D 776 S 15 20/20 Normal A1038V N/D 634 D 20 10 20/400 STGD / FFM A1038V N/D 3 F 60 60 20/20 Pigmentary abnormalities and drusen wt N/D 2 M 49 20/20 Normal A1038V N/D 615 615 S 22 8 20/200 STGD / FFM 5018 ϩ 2T 3 C N/D 616 D 23 10 20/200 STGD / FFM 5018 ϩ 2T 3 C N/D 764 D 25 20/20 Normal 5018 ϩ 2T 3 C N/D 763 F 60 20/20 Normal 5018 ϩ 2T 3 C N/D 765 M 55 55 20/20 Pigmentary abnormalities and drusen wt N/D 629 629 D 23 10 STGD / FFM E1399K N/D 622 627 D 47 12 20/400 STGD N/D N/D 622 D 35 8 20/400 STGD / FFM N/D N/D 623 C 19 10 20/200 STGD / FFM S, son; D, daughter; F, father; M, mother; C, cousin; Gm, grandmother; Gs, grandson; (p), polymorphism; wt, wild type; N/D, not determined. Login to comment 62 ABCA4 p.Val767Asp ABCA4 p.Thr897Ile ABCA4 p.Glu1399Lys Five mutations were unique for this study: missense changes V767D (exon 15), T897I (exon 18), E1399K (exon 28), insertion of four nucleotides CAAA at position 250 in exon 3, and a splice site variant 5018 ϩ 2T/C in exon 36. Login to comment 69 ABCA4 p.Gly1961Glu Of interest, the second allele in this pedigree was identified as harboring the G1961E mutation. Login to comment 70 ABCA4 p.Gly1961Glu Moreover, in the two other families heterozygous for the G1961E variant (pedigrees 624 and 636, Table 1) the age of diagnosis was 15 years or more. Login to comment 93 ABCA4 p.Gly1961Glu The previously reported G1961E mutation segregated with the disease in 3 (27%) of 11 families (Fig. 1). Login to comment 96 ABCA4 p.Gly1961Glu Although limited numbers and the relatively early age (below or near 60 years) of individuals studied prevents us from making definitive conclusions, this observation supports the association of the G1961E variant with AMD. Login to comment 97 ABCA4 p.Gly1961Glu It is of interest that in all three families segregating the G1961E allele patients were found to have Stargardt disease at the age 15 or more (Table 1). Login to comment 116 ABCA4 p.Gly1961Glu ABCA4 p.Gly1961Glu To date, no patient with STGD1 homozygous for the G1961E mutation has been identified, although this mutation is one of the most frequent in patients with STGD (Ͼ10%), and the number of screened patients with STGD1 exceeds several hundred.4,11,14 Altogether, these data allow classifying the G1961E mutation as a "mild" alteration15 and individuals homozygous for this variant may not manifest the Stargardt disease phenotype. Login to comment 119 ABCA4 p.Gly1961Glu The G1961E variant was found to be the most frequent in Italian patients with STGD, in correlation with the previous data from patient collections with different ethnic backgrounds. Login to comment